Hunt v. Secretary of Health and Human Services

Opinion

In the United States Court of Federal Claims OFFICE OF SPECIAL MASTERS Filed: May 8, 2026

* * * * * * * * * * * * * * * STEPHEN R. HUNT, * * * Petitioner, * No. 21-1379V * v. * Special Master Young * SECRETARY OF HEALTH * AND HUMAN SERVICES, * * Respondent. * * * * * * * * * * * * * * * *

Richard H. Moeller, Moore, Heffernan, et al., Sioux City, IA, for Petitioner Austin Joel Egan, United States Department of Justice, Washington, DC, for Respondent

DECISION ON ENTITLEMENT 1

On May 20, 2021, Stephen Hunt (“Petitioner”) filed a petition for compensation under the National Vaccine Injury Compensation Program (“Vaccine Act” or “the Program”), 42 U.S.C. § 300aa-10 et seq. (2018). 2 Pet., ECF No. 1. He alleged that after receipt of a pneumococcal conjugate (“Prevnar 13”) vaccine on May 21, 2018, “he experienced, and continues to experience, pain, illnesses, disabilities, injuries, and conditions which are a result of or caused in fact by the vaccine.” Id. at 1. Petitioner’s brief in support of his motion for a ruling on the record clarified that Petitioner “sustained illnesses, disabilities, injuries, and conditions, including Guillain Barré Syndrome [(“GBS”) 3], which were caused-in-fact by the Prevnar 13 vaccine.” Pet’r’s Mot., ECF No. 58 at 1. Respondent argued against compensation, asserting that Petitioner could not establish vaccine causation by a preponderance of the evidence. Resp’t’s Rept. at 11, ECF No. 31.

1 Because this Decision contains a reasoned explanation for the action taken in this case, it must be made publicly accessible and will be posted on the United States Court of Federal Claims’ website, and/or at https://www.govinfo.gov/app/collection/uscourts/national/cofc, in accordance with the E-Government Act of 2002. 44 U.S.C. § 3501 note (2018) (Federal Management and Promotion of Electronic Government Services). This means the Decision will be available to anyone with access to the internet. In accordance with Vaccine Rule 18(b), Petitioner has 14 days to identify and move to redact medical or other information, the disclosure of which would constitute an unwarranted invasion of privacy. If, upon review, I agree that the identified material fits within this definition, I will redact such material from public access. 2 National Childhood Vaccine Injury Act of 1986, Pub L. No. 99-660, 100 Stat. 3755. Hereinafter, for ease of citation, all “§” references to the Vaccine Act will be to the pertinent subparagraph of 42 U.S.C. § 300aa (2018). 3 GBS is a “rapidly progressive ascending motor neuron paralysis of unknown etiology, frequently seen after an enteric or respiratory infection.” Guillain-Barré Syndrome, DORLAND’S MED. DICTIONARY ONLINE, https://www.dorlandsonline.com/dorland/definition?id=110689 (hereinafter, “DORLAND’S”). A careful analysis and weighing of all the evidence presented in this case in accordance with the applicable legal standards 4 reveals that Petitioner has failed to provide preponderant evidence that the Prevnar 13 vaccine he received on May 21, 2018, was the cause-in-fact of his GBS. Accordingly, Petitioner is not entitled to an award of compensation.

I. Procedural History

Petitioner filed his petition, an affidavit, and medical records on May 20, 2021. Pet., Pet’r’s Exs. 1–16, ECF No. 1. Petitioner filed additional medical records and a statement of completion between July 7, 2021, and August 25, 2021. Pet’r’s Exs. 17–18, ECF No. 7; Pet’r’s Exs. 19–29, ECF No. 9; Pet’r’s Ex. 30, ECF No. 11; ECF No. 13. Petitioner filed additional medical records and another statement of completion on January 3, 2022. Pet’r’s Exs. 32–34, ECF No. 16; ECF No. 18.

On May 11, 2022, this case was referred for alternative dispute resolution (“ADR”) proceedings with Special Master Gowen. ECF Nos. 26–27. Special Master Gowen held an ADR conference between the parties on July 12, 2022, where Respondent indicated his intention to continue defending the case. See Min. Entry, docketed July 12, 2022; see also ECF No. 29. The same day Special Master Gowen entered an order removing the case from ADR and restoring it to my active docket. ECF No. 29.

Respondent filed his Rule 4(c) report, opposing compensation, on September 14, 2022. Resp’t’s Rept. Petitioner filed additional medical records on February 23, 2023. Pet’r’s Exs. 36– 41, ECF No. 35. On March 13, 2023, Petitioner filed an expert report from Lawrence Steinman, M.D., and his curriculum vitae (“CV”). Pet’r’s Exs. 42–43, ECF No. 36. Petitioner filed supporting medical literature on April 3, 2023. Pet’r’s Exs. 44–84, ECF No. 39. Respondent filed responsive expert reports from Dara Jamieson, M.D., and J. Lindsay Whitton, M.B., Ch.B., Ph.D., on September 15, 2023, along with their CVs and supporting literature. Resp’t’s Ex. A, Tabs 1–15, Resp’t’s Ex. B, ECF No. 41; Resp’t’s Ex. C, Tabs 1–33, Resp’t’s Ex. D, ECF No. 42.

Petitioner filed a supplemental report from Dr. Steinman on December 11, 2023, and supporting medical literature on December 14, 2023. Pet’r’s Ex. 85, ECF No. 44; Pet’r’s Exs. 86– 95, ECF No. 45. Respondent filed a supplemental report from Dr. Jamieson, along with supporting literature, on March 29, 2024. Resp’t’s Ex. E, Tab 1, ECF No. 46. Respondent also filed a supplemental report and supporting literature from Dr. Whitton on May 8, 2024. Resp’t’s Ex. F, Tabs 1–4, ECF No. 48. Petitioner filed a final supplemental report from Dr. Steinman and supporting literature on July 2, 2024. Pet’r’s Exs. 96–97, ECF No. 50.

On September 16, 2024, Petitioner filed a motion for a ruling on the record and additional medical literature. Pet’r’s Mot.; Pet’r’s Ex. 102, ECF No. 59. Respondent filed his response on

4 While I have reviewed all of the information filed in this case, only those filings and records that are most relevant to the Ruling will be discussed. Moriarty v. Sec’y of Health & Hum. Servs., 844 F.3d 1322, 1328 (Fed. Cir. 2016) (“We generally presume that a special master considered the relevant record evidence even though he does not explicitly reference such evidence in his decision.”) (citation omitted); see also Paterek v. Sec’y of Health & Hum. Servs., 527 F. App’x 875, 884 (Fed. Cir. 2013) (“Finding certain information not relevant does not lead to—and likely undermines—the conclusion that it was not considered.”).

2 November 12, 2024, and Petitioner filed his reply on December 4, 2024. Resp’t’s Resp., ECF No. 62; Pet’r’s Reply, ECF No. 64.

This matter is now ripe for consideration.

II. Medical Evidence

Petitioner’s pre-vaccination medical history is significant for cervical and lumbar degeneration and diabetes. Pet’r’s Ex 4 at 72; Pet’r’s Ex. 5 at 45. Petitioner received his Prevnar 13 vaccination on May 21, 2018. Pet’r’s Ex. 2 at 3. Approximately two and a half weeks later, on June 7, 2018, he presented to the Ohio Health Emergency Department (“ED”) for neck, back, and midthoracic pain. Pet’r’s Ex. 4 at 82. Petitioner described how several days prior, while planting and lifting, he experienced numbness or tingling in all four of his extremities. Id. Petitioner denied any cough, runny nose, ear pain, sore throat, recent fall, or injury. Id. Petitioner reported “significant pain,” which was “highly unusual” to him. Id. The attending physician noted that Petitioner’s computed tomography (“CT”) scan showed multiple abnormal findings, including cervical and lumbar degenerative changes, prostate enlargement, and abnormal bladder. Id. at 86.

On June 8, 2018, Petitioner returned to the ED for neck pain, back pain, numbness, tingling, and loss of strength. Pet’r’s Ex. 4 at 64. His neurological examination was marked as “normal.” Id. at 69. Physician notes mentioned Petitioner’s cervical and lumbar degenerative changes, weakness in his upper extremities, numbness in his lower extremities, and Petitioner’s inability to get comfortable. Id.at 72. Petitioner was then transferred to Riverside Methodist Hospital (“RMH”) and hospitalized until June 11, 2018. Id.; Pet’r’s Ex. 5 at 17. Upon arrival, Petitioner had full strength in all four extremities, but the nurse’s notes also recorded radiculopathy, numbness, tingling, and moderate discomfort that was worse with movement. Pet’r’s Ex. 5 at 14; Pet’r’s Ex. 6 at 16. On June 9, 2018, Petitioner underwent a neurosurgery consultation for his back pain and radiculopathy. Pet’r’s Ex. 5 at 26. Upon examination, Petitioner had intermittent numbness in both hands and feet, a negative Hoffman’s sign, and normal strength in his extremities. Id. at 28. On June 10, 2018, Petitioner underwent magnetic resonance imaging (“MRI”) of his thoracic spine, which revealed an anterior displacement of the thoracic spinal cord. Id. at 79. Later that day, a hospitalist discussed diabetes management with Petitioner and stated that diabetic neuropathy could be contributing to the pain, numbness, and tingling in his feet. Id. at 45. On June 11, 2018, a neurosurgeon reviewed the MRI and concluded that Petitioner had a T4 posterior subarachnoid cyst that was not “acutely surgical” and that Petitioner’s lower extremities were not myelopathic. Id. at 44. Later that day, Petitioner was discharged and stated his back pain was completely resolved. Id.

Petitioner returned to the ED on June 12, 2018, complaining of tingling and weakness in his upper extremities and progressive tingling and weakness in his lower extremities. Pet’r’s Ex. 4 at 34. The treating physician considered a diagnosis of GBS given the “progression of symptoms and [felt the] need to reimage for progression of compressive phenomenon as well as consideration of [GBS] or other nonmechanical etiologies of progressive lower greater than upper weakness and paresthesias.” Id. at 43. From June 13, 2018, to June 23, 2018, Petitioner was hospitalized at RMH. Pet’r’s Ex. 38 at 65; Pet’r’s Ex. 39 at 33. Upon arrival, he was too weak to walk. Pet’r’s Ex. 38 at 65. The attending physician noted Petitioner had newly onset facial droop and acute back pain in addition to twenty years of chronic back pain. Id. at 93. Petitioner underwent a brain MRI with

3 and without contrast, which showed an asymmetric effacement of the right facial nerve compatible with Bell’s palsy. 5 Pet’r’s Ex. 39 at 98. On June 14, 2018, a physiatrist performed an electromyogram (“EMG”) examination and concluded Petitioner’s condition was consistent with acute inflammatory demyelinating polyradiculopathy (“AIDP”), which is otherwise known as GBS. Pet’r’s Ex. 38 at 111, 114. The hospitalist assessed GBS and transferred Petitioner to the intensive care unit. Id. at 117.

During his hospitalization, Petitioner was seen by neurologist Dr. Jacqueline Nicholas. Pet’r’s Ex. 38 at 65. She agreed with his AIDP/GBS diagnosis and added that “[h]is [r]ight facial weakness raises consideration of possible Miller Fisher Variant,[6] Bickerstaff encephalitis.” Id. She planned to treat “the AIDP and [f]acial palsy as one and not separate out the facial weakness as [B]ell’s palsy.” Id. at 66. In her assessment, Dr. Nicholas noted that Petitioner had a recent urinary tract infection (“URI”) and Prevnar 13 vaccination prior to presenting to the hospital with mid-back pain. She noted that his AIDP “could explain his radicular back pain.” Id.

Petitioner’s consulting neurologist reviewed Petitioner’s MRI imaging and EMG study and concluded that the imaging and studies suggested GBS. Pet’r’s Ex. 38 at 119–20. A lumbar puncture was performed, and intravenous immunoglobulin (“IVIG”) was ordered pending the results of Petitioner’s IgA levels. Id. at 122; Pet’r’s Ex. 39 at 100. The nurse practitioner also noted the etiology of Petitioner’s right Bell’s palsy was a “recent [URI], possible extension of AIDP. Facial nerve involvement noted on EMG and thought to be part of AIDP.” Pet’r’s Ex. 38 at 122. IVIG was initiated, and on June 16, 2018, the neurologic nurse practitioner noted Petitioner showed improved strength in his upper extremities but remained weak in his lower extremities. Id. at 129. Petitioner could not dorsiflex his toes, and his reflexes remained absent in his lower extremities and were diminished in his upper extremities. Id. at 131. Petitioner reported his back pain improved, and the neurology nurse practitioner attributed the back pain to AIDP. Id. at 128– 29.

On June 17, 2018, Petitioner received his cerebrospinal fluid (“CSF”) tests results from his lumbar puncture, which included the presence of xanthochromia, elevated protein, and elevated white blood cells. Pet’r’s Ex. 39 at 40–42. The neurologist concluded that Petitioner had AIDP but was unsure of the etiology of Petitioner’s right facial weakness, noting the possibility of Bell’s palsy, the Miller Fisher variant of GBS, and Bickerstaff encephalitis. Id. at 142. The neurologist also concluded that, based upon the xanthochromia found in the CSF, Petitioner had a thoracic arachnoid web. Id.

On June 19, 2018, the neurologic nurse practitioner noted Petitioner’s strength was slowly improving, and Petitioner completed his fifth and final dose of IVIG. Pet’r’s Ex. 38 at 149. Petitioner’s prior medical history on a June 20, 2018 visit record noted that Petitioner had a recent URI and a pneumonia vaccine on May 21, 2018. Id. at 159. During the examination, Petitioner had no movement in his feet, trace movement in the hips and knees, and weak movement in the upper extremities and shoulders. Id. at 161. On June 21 and June 22, 2018, occupational therapists evaluated Petitioner for discharge to inpatient rehabilitation. Pet’r’s Ex. 39 at 17, 21. The

5 Bell palsy is “unilateral facial paralysis of sudden onset, due to lesion of the facial nerve and resulting in characteristic distortion of the face.” Bell Palsy, DORLAND’S. 6 Miller Fisher Syndrome is “a variant of [GBS] characterized by areflexia, ataxia, and ophthalmoplegia.” Fisher Syndrome, DORLAND’S. 4 occupational therapists noted that Petitioner needed assistance for many activities of daily living. Id. at 17–18, 21–22. By June 23, 2018, Petitioner’s GBS had improved following treatment, and he was discharged to inpatient rehabilitation. Id. at 32–33. Petitioner’s discharge diagnoses were AIDP, right facial weakness, hyponatremia, posterior arachnoid cyst, encephalopathy, hypertensive urgence, constipation, and Type 2 diabetes mellitus. Id. Petitioner was admitted to Ohio Health Rehabilitation Hospital on the night of June 23, 2018, for GBS, weakness, and numbness. Pet’r’s Ex. 10 at 175. The physical medicine and rehabilitation specialist noted Petitioner’s GBS was past its nadir and Petitioner was improving clinically. Id. at 178.

On October 30, 2018, Petitioner saw neurologist Douglass Woo for his AIDP. Pet’r’s Ex. 18 at 46. Petitioner’s facial weakness resolved but still had significant weakness in his legs. Id. In his impression of Petitioner’s AIDP, Dr. Woo stated that it was idiopathic, closely improving, and would continue to be monitored. Id. at 45. On February 21, 2019, Petitioner returned to Dr. Woo, who noted Petitioner demonstrated steady improvement since his visit in October. Id. at 34. Dr. Woo stated that Petitioner’s AIDP “remain[ed] idiopathic,” continued to improve, and would continue to be monitored. Id. at 30. On June 29, 2020, Petitioner saw an oncologist for his sepsis, and his medical history noted Petitioner’s history of GBS that was preceded by his Prevnar13 vaccination. Pet’r’s Ex. 3 at 12. Under “Allergens,” the oncologist listed “Prevnar 13 – [GBS].” Id. at 14.

No other relevant medical records were filed.

III. Petitioner’s Affidavit

On May 20, 2021, Petitioner filed a brief affidavit. Pet’r’s Ex. 1. He recounted receipt of his Prevnar 13 vaccine on May 21, 2018, at seventy years old. Id. at ¶ 2. Shortly thereafter, “[s]ometime during the Memorial Day weekend, [Petitioner and his wife] were visiting at the home of [his brother-in-law] when [he] felt numbness in [his] calves and lower legs, and tingling in [his] feet.” Id. at ¶ 3. The next morning, Petitioner’s legs gave out and a few days later, the numbness and tingling in his legs continued to progress and then it started in his hands. Id. at ¶ 4. Petitioner recalled being taken to the ED on or about June 5, 2021, and staying overnight. Id. at ¶ 5. He went to several emergency rooms over a period of weeks in June and was eventually told that he had GBS during his hospitalization at RMH. Id. at ¶¶ 6–9.

Following his diagnosis, Petitioner underwent inpatient rehabilitation and various therapies, including physical, occupational, and speech. Pet’r’s Ex. 1 at ¶¶ 10–13. Prior to his vaccination, Petitioner described himself as “in generally good health and physically fit.” Id. at ¶ 17.

IV. Experts

A. Expert Qualifications

1. Petitioner’s Expert, Dr. Lawrence Steinman, M.D.

Dr. Steinman is a board-certified neurologist and currently serves as a Professor of Neurology at Stanford University. Pet’r’s Ex. 42 at 1. He received his M.D. from Harvard

5 University and completed his medical internship and residencies in pediatric and adult neurology at Stanford University Hospital. Pet’r’s Ex. 43 at 1. Throughout his clinical career Dr. Steinman has “cared for hundreds of adults and children with various forms of inflammatory neuropathy,” including GBS. Pet’r’s Ex. 42 at 1. Dr. Steinman has published 12 articles in the field of molecular mimicry, in addition to numerous other publications. Id. He has also received several awards for his work in the field of neuro-immunology. Id. at 2–4.

2. Respondent’s Expert, Dr. Dara Jamieson, M.D.

Dr. Jameison is a board-certified neurologist and currently serves as a Clinical Associate Professor of Neurology at Weill Cornell Medicine. Resp’t’s Ex. A at 1. She received her M.D. from the University of Pennsylvania School of Medicine, where she also completed her medical internship, neurology residency, and research fellowship. Resp’t’s Ex. B at 1. She has over 30 years of clinical neurology experience and has “authored many papers published in peer reviewed journals, and authored two books, as well as book chapters and review articles of multiple neurological topics.” Resp’t’s Ex. A at 1–2.

3. Respondent’s Expert, Dr. J. Lindsay Whitton, M.B., Ch.B., 7 Ph.D.

Dr. Whitton is an Emeritus Professor of the Department of Immunology and Microbiology at the Scripps Research Institute in La Jolla, California. Resp’t’s Ex. D at 1. He is not licensed to practice in the United States and is not board-certified in the United States. Resp’t’s Ex. C at 3. He received his M.B., Ch.B. and Ph.D. in virology from the University of Glasgow. Resp’t’s Ex. D at 1. Throughout his career he has held several academic teaching and research positions in the United Kingdom and in the United States. Id. He has also “published both on the adaptive and innate immune responses, and on molecular mimicry.” Resp’t’s Ex. C at 1.

B. Expert Reports

1. Diagnosis

Petitioner’s diagnosis was confirmed throughout the medical records. See generally, Pet’r’s Exs. 6, 7, 38. Additionally, Petitioner’s expert, Dr. Steinman and Respondent’s expert, Dr. Jamieson, both agreed that Petitioner suffered from AIDP consistent with GBS. Pet’r’s Ex. 42 at 42, Resp’t’s Ex. A at 11. In his initial expert report, Dr. Steinman asserted that “[b]ased on the medical record and opinions of the treating physicians the diagnosis here is [GBS].” Id. at 14. Dr. Steinman referenced an explanation from The National Institute of Neurological Disorders and Stroke that in GBS patients, “the immune system starts to destroy the myelin sheath that surrounds the axons of many peripheral nerves, or even the axons themselves.” Pet’r’s Ex. 42 at 14 (citing Pet’r’s Ex. 52). 8 Dr. Jamieson agreed that “it is more likely than not that [Petitioner] had GBS/AIDP.” Resp’t’s Ex. A at 11. In her initial report, Dr. Jamieson also defined GBS and explained that it is “a group of autoimmune disorders that present as an acute, monophasic illness and that cause neurological deficits due to peripheral nerve injury.” Id. at 6. Dr. Jamieson continued that AIDP is the most common subtype of GBS, and it is characterized by “progressive,

7 An M.B., Ch.B., is the United Kingdom equivalent to an M.D. in the United States. 8 Guillain-Barré Syndrome Fact Sheet, NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE, https://www.ninds.nigh.gov/disorders/gbs/detail_gbs.htm (last visited April 3, 2023). 6 symmetric, leg followed by arm, distal to proximal, weakness with absent or depressed deep tendon reflexes.” Id.

2. Causation

a. Dr. Steinman’s Initial Report

Dr. Steinman explained that the National Institute of Neurological Disorders and Stroke defines GBS as a rare syndrome that usually “occurs a few days or weeks after the patient has had symptoms of a respiratory or gastrointestinal viral infection.” Pet’r’s Ex. 42 at 14. He noted that occasionally, it is triggered by surgery and “[i]n rare instances vaccinations may increase the risk of GBS.” Id. Acknowledging that Petitioner’s medical records mention a recent URI, Dr. Steinman asserted that otherwise they do not “provide any detail of a diagnosis of [URI] or illness temporally related to the onset of AIDP.” Id. He continued that “[t]he only record of [a URI], before the onset of AIDP, appears to be [from a medical visit] on March 15, 2018, [67] days prior to vaccination and approximately 11 to 12 weeks prior to onset of AIDP.” Id.

The 17-day interval between Petitioner’s Prevnar 13 vaccine and the onset of his GBS symptoms is more indicative, according to Dr. Steinman, of a causal relationship based on a “study from [the Centers for Disease Control (“CDC”)] on the swine flu vaccine and GBS.” Pet’r’s Ex. 42 at 42 (citing Pet’r’s Ex. 84). 9 This seminal 1979 paper by the CDC revealed epidemiologic evidence that “[w]hen compared to the unvaccinated population, the vaccinated population had a significantly elevated attack rate in every adult age group.” Pet’r’s Ex. 84 at 1. Dr. Steinman extrapolated that paper’s findings of a “period of increased risk [] concentrated primarily within the [five]-week period after vaccination,” to identify an appropriate temporal relationship between Prevnar 13 vaccination and GBS. Id. Dr. Steinman compared this five-week period to the findings in the Haber et al. 10 paper that documented 11 cases of GBS following Prevnar 13 vaccination. Pet’r’s Ex. 83. The symptom onset interval was two to 43 days with a median of nine days. Id. at 4. Dr. Steinman noted that of the 11 patients, only one “had [a URI] 16 days prior to GBS.” Pet’r’s Ex. 42 at 42. Ultimately, the researchers concluded that “evidence of a possible association of GBS with inactivated seasonal influenza vaccines has been inconsistent[, and] data mining analysis noted no disproportionate reporting for GBS.” Pet’r’s Ex. 84 at 5. However, Dr. Steinman argued that Petitioner’s chronology is consistent with the timing for the interval between vaccination and GBS in the 1976 swine flu studies, and “[a] a showing of a proximate temporal relationship between vaccination and injury is fulfilled.” Pet’r’s Ex. 42 at 42.

Dr. Steinman opined that Petitioner’s GBS was caused by his Prevnar 13 vaccine via molecular mimicry. Pet’r’s Ex. 42 at 11. Referring to a self-authored article in 1993, he explained that generally during this process, “shared structures on a virus or bacteria or in a vaccine can trigger a cross-reactive response to self.” Id. at 15 (citing Pet’r’s Ex. 48). 11 Dr. Steinman identified

9 Lawrence B. Schonberger et al., Guillain-Barre Syndrome Following Vaccination in the National Influenza Immunization Program, United States, 1976–77, 110 AM. J. EPIDEMIOLOGY 105 (1979). 10 Penina Haber et al., Post-Licensure Surveillance of 13-Valent Pneumococcal Conjugate Vaccine (PCV13) in Adults Aged ≥ 19 Years Old in the United States, Vaccine Adverse Event Reporting System (VAERS), June 1, 2012–December 31, 2015, 34 VACCINE 6330 (2016). 11 Lawrence Steinman, The Discovery of Natalizumab, A Potent Therapeutic for Multiple Sclerosis, 199 J. Cell Biology 413 (2012). 7 several potential cross-reactive components of the Prevnar 13 vaccine, including the CRM197 carrier protein, polysorbate 80, a succinate buffer, an aluminum phosphate adjuvant, and two of the 13 Streptococcus pneumoniae serotypes, specifically the 18C and 23F saccharides. 12 Id. at 16. He explained that the 18C capsular polysaccharide, 13 for example, contains a glycerol-phosphate14 group that “must be preserved for conserving adequate antigenicity of the [serotype] within the Prevnar 13 vaccine.” Id. at 19.

As evidence of homology sufficient for cross reactivity between vaccine and host components, Dr. Steinman cited to multiple sclerosis 15 (“MS”) studies to explain that “phospholipids[16] are components of the myelin sheath in humans, and [] they are targeted by antibodies in neuroinflammation.” Pet’r’s Ex. 42 at 16. He continued that he and other researchers had “identif[ied] bona fide lipid targets of the autoimmune response in [a human] MS brain, and an animal model of MS to explore the role of identified lipids in autoimmune demyelination.” Id. For example, Kanter et al., 17 which includes Dr. Steinman as a co-author, is styled as a “large- scale multiplex analysis of antibody responses to lipids in [MS].” Pet’r’s 50 at 1. The authors sought to “show that antibodies to sulfatide and other lipids are present in CSF samples from individuals with [MS] and in sera from mice with experimental autoimmune encephalitis [(“EAE”)].” Id. Their “observations suggest that autoimmune responses directed against sulfatide[18] and other lipids contribute to the pathogenesis of autoimmune demyelinating disease.” Id. at 5. Dr. Steinman also cited the Ho et al. 19 article asserting “that ‘[l]ipids constitute 70% of the myelin sheath, and autoantibodies against lipids may contribute to the demyelination that characterizes [MS].’” Pet’r’s Ex. 42 at 16. (quoting Pet’r’s Ex. 51 at 1). Further, the authors were able “to identify bona fide lipid targets of the autoimmune response in MS brain,” specifically, a phosphate group in phosphatidylserine 20 and oxidized phosphatidylcholine 21 derivatives. Id. Dr.

12 A saccharide is “one of a series of carbohydrates, including the sugars. The saccharides are divided into monosaccharides, oligosaccharides, and polysaccharides, according to the number of monosaccharaide groups [] composing them.” Saccharide, DORLAND’S. A monosaccharide is “a simple sugar; a carbohydrate that cannot be decomposed by hydrolysis.” Monosaccharide, DORLAND’S. 13 A polysaccharide is “a carbohydrate that on hydrolysis yields a large number of monosaccharides (variously defined as five or more to eleven or more).” Polysaccharide, DORLAND’S. 14 Glycerol Phosphate is “an intermediate in the glycerol phosphate shuttle, in the utilizations of glycerol, and in the biosynthesis of lipids.” Glycerol Phosphate, DORLAND’S. 15 MS is “a disease in which there are foci of demyelination throughout the white matter of the central nervous system, sometimes extending into the gray matter.” Multiple Sclerosis, DORLAND’S. 16 A phospholipid is “any lipid that contains phosphorus, including those with a glycerol backbone.” Phospholipid, DORLAND’S. 17 Jennifer L. Kanter et al., Lipid Microarrays Identify Key Mediators of Autoimmune Brain Inflammation, 12 NATURE MEDICINE 138 (2006). 18 Sulfatide are “any of the cerebrosides esterified with a sulfate residue at the C-6 of the sugar; they are found largely in the medullated nerve fibers.” Sulfatide, DORLAND’S. 19 Peggy P. Ho et al., Identification of Naturally Occurring Fatty Acids of the Myelin Sheath That Resolve Neuroinflammation, 4 SCI. TRANSNAT’L MED. 73 (2012). 20 Phosphatidylserine is “a phospholipid in which serine is attached to the phosphate group of phosphatidic acid by an ester linkage . . . and is localized preferentially in the inner surface of the plasma membrane.” Phosphatidylserine, DORLAND’S. 21 Phosphatidylcholine is “a phospholipid in which choline is attached to the phosphate group of phosphatidic acid by an ester linkage . . . and is localized preferentially in the outer surface of the plasma membrane.” Phosphatidylcholine, DORLAND’S. 8 Steinman then cited to Nakos et al. 22 and noted that “phospholipid antibodies were found in patients with GBS,” but not in the controls. Id. (citing Pet’r’s Ex. 55).

The Nakos et al. article noted that GBS “is an acute inflammatory polyneuropathy related to autoimmunity. However, no conclusive etiological concept has yet been found.” Pet’r’s Ex. 55 at 1. The authors sought to measure antibodies levels before, during, and after treatment to determine useful indicators of treatment efficacy. Id. Noting the “close association between GBS and preceding infection,” the article stated that “[a]pproximately 15–50% of patients with GBS develop anti-gangliosidic antibodies that target glycolipids.” 23 Id. at 2. The authors stated that “[l]ipopolysaccharides[24] of [Campylobacter jejuni (“C. jejuni”)] share structural similarity with epitopes in gangliosides,” 25 and suggest cross-reactivity could occur between antibodies against the bacteria and host myelin sheaths. Id. The study revealed “a wide range of anti-phospholipid antibodies in patients with idiopathic GBS,” and the authors stressed the importance of an investigation into this relationship. Id. at 5.

Dr. Steinman also cited to Chang et al., 26 which noted that “phosphoglycerol is present in serotypes 18C and in 23F in the Prevnar 13 vaccine.” Pet’r’s Ex. 42 at 20 (citing Pet’r’s Ex. 56). Dr. Steinman asserted that “phosphoglycerol is directly targeted by the core of the two human antibodies targeting 23F.” Pet’r’s Ex. 42 at 21. He inserted two schematics of 23F into his report with the phosphoglycerol central to the antibody binding site identified. The first figure is reproduced from the Bryson et al. 27 article. See Pet’r’s Ex. 59. The second was taken from Yu et al. 28 See Pet’r’s Ex. 60.

22 G. Nakos et al., Anti-Phospholipid Antibodies in Serum From Patients with Guillain-Barré Syndrome, 31 Intensive Care Med. 1401 (2005). 23 A glycolipid is “a lipid containing carbohydrate groups, usually galactose but also glucose, inositol, or others . . . the term is used almost exclusively to denote the sphingosine derivatives lacking phosphate groups.” Glycolipid, DORLAND’S. 24 A lipopolysaccharide is “a complex of lipid and polysaccharide” and “a major component of the cell wall of gram-negative bacteria.” Lipopolysaccharide, DORLAND’S. 25 A ganglioside is “any group of glycosphingolipids in which the polar head group on ceramide is a sialic acid-containing oligosaccharide linked via glucose residue; they occur predominantly in tissues of the [CNS].” Ganglioside, DORLAND’S. 26 Janoi Chang, Relevance of O-Acetyl and Phosphoglycerol Groups for the Antigenicity of Streptococcus Pneumoniae Serotype 18C Capsular Polysaccharide, 30 Vaccine 7090 (2012). 27 Steve Bryson et al., Structures of Preferred Human IgV Genes-Based Protective Antibodies Identify How Conserved Residues Contact Diverse Antigens and Assigned Source of Specificity to CDR3 Loop Variation, 196 J. IMMUNOLOGY 4723 (2016). 28 Kang Yu et al., Synthesis of the Biological Repeating Unit of Streptococcus Pneumoniae Serotype 24F Capsular Polysaccharide, 14 ORGANIC & BIOMOLECULAR CHEMISTRY 11462 (2016). 9 Pet’r’s Ex. 59, Figure 2; Pet’r’s Ex. 60, Figure 1.

Yu et al. explained and illustrated “[a]n efficient synthesis of the 3-aminopropyl glycoside[29] of the biological repeating unit of Streptococcus pneumoniae serotype 23F capsular polysaccharide.” Pet’r’s Ex. 60 at 1. This breakthrough, the authors opined, “has laid the foundation for accessing homogeneous and structurally well-defined bacterial [capsular polysaccharide] analogs . . . useful for structure–activity relationships and many other biological studies.” Id. at 4. Bryson et al. “illuminate[d] the centrality of the phosphate in glycerophosphate in a human antibody response to 23F after the human received a pneumococcal vaccine intended to elicit antibodies to 23F[, but t]he study was done with Pneumovax 23.” Pet’r’s Ex. 42 at 24 (citing Pet’r’s Ex. 59). Dr. Steinman asserted that the “data from the Bryson [et al.] article demonstrates UNEQUIVOCALLY that the immune response to the serotype 23F component of Pneumovax 23 targets the phosphoglycerol in serotype 23F.” Id. at 24 (emphasis in original). He acknowledged that Pneumovax 23 is a different vaccine but asserted that Prevnar 13 contains the same sugars as Pneumovax 23. Id. He mused that “[if] only there were such pictures with a study on Prevnar 13, it would be a ‘perfect fit,’ but [asserted that] in searching for evidence that is ‘sound and reliable,’ this is the best the Petitioner can do at the present time. Id. Dr. Steinman then argued that “Prevnar 13 is also designed to generate an immune response to serotype 23F.” Id. He concluded that “[s]ince the 23F and 18C components of Prevnar 13 also contain[] the phosphoglycerol moiety[30] that is targeted by the antibodies generated by Pneumovax, it is very likely that the immune response to 23F and 18C components of Prevnar 13 vaccine also targets the phosphoglycerol moiety.” Id. at 24–25.

Dr. Steinman identified CRM197 as one part of a second molecular mimicry homology. Pet’r’s Ex. 42 at 25. CRM197 is “used to conjugate the pneumococcal polysaccharides in the Prevnar 13 vaccine to an immunogenic protein carrier.” Id. Dr. Steinman then identified contactin- 1 as the potential target, based on the Devaux et al. 31 paper that found “[i]n eight patients with GBS or CIDP, we identified that IgG antibodies recognized the native extracellular domain of NF186, gliomedin, or contactin.” Id. (citing Pet’r’s Ex. 63) The National Library of Medicine defines contactin-1 as a “glycosylphosphatidylinositol-anchored neuronal membrane protein that

29 A glycoside is “any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible by hydrolytic cleavage, into sugar and a nonsugar component (aglycon), and named specifically for the sugar contained, as glucoside (glucose).” Glycoside, DORLAND’S. 30 A moiety is defined as “any equal part; a half; also any part or portion.” Moiety, DORLAND’S. 31 Jerome Devaux et al., Nodal Proteins are Target Antigens in Guillain-Barré Syndrome, 17 J. PERIPHERAL NERVOUS SYSTEM 62 (2012). 10 functions as a cell adhesion molecule. It may play a role in the formation of axon connections in the developing nervous system.” 32

The Devaux et al. study sought to “investigate[] the prevalence of antibodies against nodal adhesion molecules in patients with GBS or chronic inflammatory demyelinating polyneuropathy (“CIDP”).” Pet’r’s Ex. 63 at 1. The study “identified NF186, gliomedin, and contactin as the immune targets of autoantibodies.” Id. at 6. The authors further suggested that “autoantibodies to nodal adhesion molecules are more prevalent in GBS forms and are not related to secondary immune reactions against demyelinated or damaged myelinated fibers.” Id. at 8. The results indicated that “the prevalence of these autoantibodies in [MS] may vary considerably.” Id. Additionally, the authors warned that “[t]he causes generating these autoantibodies in GBS remain [] unknown.” Id. While “[t]he presence of autoantibodies did not correlate with any antecedent illnesses in particular,” the authors noted “that infectious agents showing molecular mimicry with nodal proteins may trigger the development of autoantibodies against NF186/gliomedin/contactin/NrCAM and simultaneously the development of IgM against gangliosides.” Id. They then warned that they “did not detect IgM deposition at nodes or paranodes, albeit many patients showed IgM antibodies against gliomedin, NF186, contactin, or NrCAM. The importance of IgM against nodal adhesion molecules in GBS pathology is therefore uncertain.” Id.

Dr. Steinman “used the NIH BLAST search tool and performed BLAST searches to align contactin-1 with the components of the CRM197” in Prevnar 13. Pet’r’s Ex. 42 at 25. The parameters that Dr. Steinman set for the search were based on his on research that demonstrated “a viral peptide with homology at just [five] amino acids with a self-peptide can induce clinical signs of EAE in mice,” even when nonconsecutive, “but there cannot be a gap in the alignment of the proteins on the BLAST search.” Id. Dr. Steinman again relied on research done in the context of MS to show how “a molecular mimic between EBNA1[, Epstein-Barr virus (“EBV”) transcription factor] and a [central nervous system (“CNS”)] protein called GlialCAM, triggers” the disease. Id. at 26. The identified homology consisted of “a stretch of 12 amino acids where there are five” that are identical. Id. at 27. The results of the CRM197 and contactin-1 BLAST revealed “[t]he sequence WEQAKALSVE has five of [10] identical amino acids, and thus would be a region that [Gautam et al. (1992), 33 Gautam et al. (1994), 34 Gautam et al. (1998), 35 and Lanz et al. 36] indicate might be capable of inducing a neuroinflammatory disease.” Id. at 32. (citing Pet’r’s Exs. 21–24).

32 CNTN1 Contactin 1 [Homo Sapiens (Human)], National Library of Medicine, https://www.ncbi.nlm. nih.gov/gene/1272 (last visited May 1, 2026). 33 Anand M. Gautam et al., A polyalanine Peptide Containing Only Five Native Myelin Basic Protein Residues Induces Autoimmune Encephalomyelitis, 176 J. EXPERIMENTAL MED. 605 (1992). Although Dr. Steinman drew conclusions from this article, it was not filed by Petitioner. Instead, Petitioner filed a screenshot of one table from this article and filed it as Petitioner’s Exhibit 21. 34 Anand M. Gautam et al., Minimum Structural Requirements for Peptide Presentation by Major Histocompatibility Complex Class II Molecules: Implications in Induction of Autoimmunity, 91 IMMUNOLOGY 767 (1994). 35 Anand M. Gautam et al., A Viral Peptide with Limited Homology to a Self Peptide Can Induce Clinical Signs of Experimental Autoimmune Encephalomyelitis, 161 J. IMMUNOLOGY 60 (1998). 36 Tobias V. Lanz et al., Clonally Expanded B Cells in Multiple Sclerosis Bind EBV EBNA1 and GlialCAM, 603 NATURE 321 (2022). 11 Following his BLAST search, Dr. Steinman cross-referenced the relevant results to the Immune Epitope Database (“IEDB”) and Alignment Resource, both publicly available online. Pet’r’s Ex. 42 at 32. He described the IEDB as a “freely available resource funded by NIAID. It catalogs experimental data on antibody and T cell epitopes studied in humans, non-human primates, and other animal species in the context of infectious disease, allergy, autoimmunity, and transplantation.” Id. Dr. Steinman noted that the sequence he identified, WEQAKALSVE, “is an epitope in diphtheria toxin, which has only one amino acid difference from CRM197.” Id. at 33. He continued that “[h]umans have been shown to mount T cell responses to these regions of the diphtheria molecule.” Id. at 35. Dr. Steinman summarized his process:

These congruent findings between 1) Petitioner’s various searches on public databases, 2) the three steps of filtration using peer reviewed journals as one criterion, 3) searches on different US government-financed search tools (BLAST, and IEDB), and now step 4) showing a correlation with detailed studies on the human immune response to diphtheria toxin, differing in only one amino acid from CRM, continue to make a compelling theory, that is sound and reliable, for how molecular mimics in Prevnar 13 can cause GBS.

Id. at 36.

Additionally, Dr. Steinman discovered “an alignment between the CRM197 component of the Prevnar 13 vaccine and Caspr2, an antigen targeted in GBS.” Pet’r’s Ex. 42 at 36. A second BLAST search comparing diphtheria toxin and Caspr2 revealed a region sharing seven of nine identical amino acids. Id. at 37. Dr. Steinman concluded that phosphoglycerol and a CRM197 region are two molecular mimics in the Prevnar 13 vaccine.

In anticipation of criticisms of his theory by Respondent’s expert(s), Dr. Steinman included a “frequently asked questions” section to his initial report. Pet’r’s Ex. 42 at 39. First, he explained why, under this theory, “the immune system would target phosphoglycerol in peripheral nerves and not in other places where it is present in the body.” Id. Dr. Steinman noted that “antibody to gangliosides results in GBS in some individuals, even though gangliosides are all over the body.” Id. He continued that when GBS manifests following C. jejuni infection, the immune system responds to gangliosides in the peripheral nervous system and “not to any diseases of erythrocytes, intestine, liver, spleen and/or testis.” Id.

b. Dr. Whitton’s Initial Report

Dr. Whitton began by defining relevant terms and explaining general processes. Resp’t’s Ex. C at 3. He characterized the structure of S. pneumoniae as a bacterial pathogen “surrounded by a capsule made up of [sugar molecules]” and the Prevnar 13 vaccine as protection against 13 of the near 100 strains of pneumococcus. Id. He continued that these sugars, known as polysaccharides when they are linked in molecules of 12 more together, are extremely diverse and occur in mammals, plants, and bacteria. Id. Their diversity is rooted in the relatively large number of monosaccharides, similar to protein chains where there are 20 different amino acid building blocks. Id. at 4. An important difference between proteins and sugars however, Dr. Whitton asserted, is “the chemical nature of their linkages.” Id. Unlike amino acid chains that are always built head-to-tail in a chain, “monosaccharides can join to each other in different molecular

12 orientations.” Id. This results in an exponentially larger number of ways to connect the same components. Id. Dr. Whitton then explained the difference between proteins and polysaccharides by comparing the former to a string of pearls and the later to branches of a tree. Id. He wrote, “each monosaccharide has several different points at which it can link to other monosaccharides; thus, not only can they build an up/down zigzagging chain, they also can grow branches; and each branch can itself sprout ‘daughter’ branches.” Id.

Next, Dr. Whitton noted the importance of the differences in the molecular composition of each of the 13 polysaccharides comprising Prevnar 13. Resp’t’s Ex. C at 5. Each of “these different bacterial polysaccharides trigger different immune responses and, consequently, our immune system can distinguish among the many different strains of S. pneumoniae based on the polysaccharides that each strain has in its capsule.” Id. This is why Prevnar 13, for example, only protects against 13 specific strains. Id. Dr. Whitton asserted that many factors determine the virulence of a bacterial pathogen; “most relevant to matter at hand, one factor that is related to virulence is the polysaccharide capsule by which each bacterium is surrounded.” Id. Because each strain has a different capsule, these “difference[s] form the basis by which the many different pneumococcal strains are distinguished.” Id. These strains are referred to as serotypes, based on “how it is recognized by the antibody response.” Id.

So, if you take a single S. pneumoniae bacterium, the antibody response against the capsule of that bacterium recognizes only that bacterium and its progeny (so, we could define that bacterium as “serotype #1” pneumococcus). However, those antibodies would not recognize other strains of S. pneumoniae that carry different polysaccharide capsules. The converse also holds true; antibodies against a different S. pneumoniae isolate would define that bacterium as “serotype #2” and those antibodies would not recognize bacteria of serotype #1 (nor bacteria of serotypes #3, #4, etc...).

Id.

Dr. Whitton cited two articles, Haber et al. and Tseng et al., 37 to highlight the safety of Prevnar 13. Resp’t’s Ex. C at 7. Haber et al. was described by the authors as “the first post- marketing safety review of [Prevnar 13] in adults.” Resp’t’s Ex. A, Tab 5 at 4. The study reviewed Vaccine Adverse Events Reporting System (“VAERS”) submissions based on an inoculation period that covered approximately 16 million vaccine doses. Id. There were 11 reports of verified GBS “with symptom onset within 42 days of [Prevnar 13] vaccination.” Id. The Tseng et al. cohort study examined adults at least 65 years of age “for risk of adverse events requiring medical attention following vaccination with [Prevnar 13] as compared with vaccination with [Pneumovax 23].” Resp’t’s Ex. A, Tab 13 at 1. A review of “313,136 doses of [Prevnar 13] and 232,591 doses of [Pneumovax 23]” revealed four adverse events of GBS following the former group and eight following the later. Id. at 4, 6. These “results indicate that there is no significantly elevated risk of [GBS].” Id. at 7. Dr. Whitton also summarized the Baxter et al. 38 study that was “not directly evaluating Prevnar 13, [but] did include two vaccines (Tdap and Td) that contain diphtheria toxin

37 Hung Fu Tseng et al., Pneumococcal Conjugate Vaccine Safety in Elderly Adults, 5 OPEN FORUM INFECTIOUS DISEASES 100 (2018). 38 Roger Baxter et al., Lack of Association of Guillain-Barré Syndrome With Vaccinations, 57 CLINICAL INFECTIOUS DISEASES 197 (2013). 13 (DT), and the authors found no association with an increased risk of GBS.” Resp’t’s Ex. C at 8 (citing Resp’t’s Ex. A, Tab 1). A study of 415 GBS patients did not find “an association between influenza vaccine or any other vaccine and development of GBS withing six weeks following vaccination.” Resp’t’s Ex. A, Tab 1 at 8. The article did note that the authors “had limited power to fully assess the risk of GBS following vaccination due to the rarity of the outcome.” Id.

According to Dr. Whitton, Dr. Steinman’s two asserted causation theories “depend on molecular mimicry.” Resp’t’s Ex. C at 12. Dr. Whitton distilled molecular mimicry down to three steps: 1) an induced immune response, 2) a cross-reaction to host material, and 3) pathogenesis. Resp’t’s Ex. C at 12–13. While acknowledging that molecular mimicry does occur, particularly in animals, Dr. Whitton quoted expert immunologist Dr. Noel Rose: “There are, however, no clear examples of a human disease caused by molecular mimicry.” Id. at 14. Dr. Whitton explained how difficult it was to cause disease this way in mice, including the need for predisposed mice that were bred because “they mounted a strong immune response to the viral protein.” Id. at 15.

In the context of this case, Dr. Whitton noted that in Prevnar 13, two of “S. pneumoniae polysaccharides [(18C and 23F)] contain modifications, [specifically] the chemical linkage of . . . a small molecule named glycerophosphate/phosphoglycerol.” Resp’t’s Ex. C at 20.

Because Dr. Steinman’s primary causation theory relies on the cross reactivity of phosphoglycerol, Dr. Whitton thought it important to discuss generally. Resp’t’s Ex. C at 17. He provided a figure of the chemical structure of phosphoglycerol and noted its very small size. Id. With an average mass of approximately 154 Da, it is incredible that a single phosphoglycerol molecule could trigger an immune response, given that “the rule of thumb is that the cutoff is about 3000 Da.” Id. Dr. Whitton then explained that small molecules (hapten) can trigger an immune response to produce antibodies if they are attached to a larger “carrier” molecule. Id. A bacterial polysaccharide is such a carrier, whereby “the epitope recognized by such an antibody would not be phosphoglycerol alone; rather, it would be a larger structure comprising phosphoglycerol + bacterial polysaccharide.” Id. Dr. Whitton then noted that in the Bryson et al. article, the authors noted the high specificity of the antibodies detected. Id. at 18. He argued that these antibodies “are not specific for phosphoglycerol alone (as Dr. Steinman appears to imply), they are specific for a larger epitope that comprises phosphoglycerol + 23F polysaccharide.” Id. By way of illustration, Dr. Whitton reproduced a figure from Bryson et al. that “showed the points of electrostatic contact between individual amino-acids on the antibody, and components of the 23F epitope.” Id. at 19. He noted that “of the nine contact points between the antibody and the epitope, eight are between various amino acids in the antibody, and the saccharide residues on the 23F structure.” Id. The only contact between the antibody and the phosphoglycerol “contacts an oxygen atom that is attached to the phosphate.” Id. Dr. Whitton asserted that these antibodies “recognize mainly the sugar residue” and only on 23F, “but not the 18C polysaccharide, even though it also has an attached phosphoglycerol. Id. He further noted that other S. pneumoniae strains, such as 11A and 15B also contain phosphoglycerol-containing polysaccharides. Id. at 20.

He summarized Dr. Steinman’s first theory of causation as follows: “(i) a phosphoglycerol- containing polysaccharide in Prevnar 13 induces an antibody response against the phosphoglycerol, and (ii) this antibody causes GBS.” Resp’t’s Ex. C at 6. As an initial matter, Dr. Whitton noted that these phosphoglycerol-containing polysaccharides are also present in S. pneumoniae; therefore for Dr. Steinman’s theory to be valid, “S. pneumoniae strains 18C and 23F

14 should cause GBS.” Id. Dr. Whitton argued that this extrapolation does not hold and cited to writing by Dr. Eric Gershwin that discusses infectious triggers of GBS. Id. at 9 (citing Resp’t’s Ex. C, Tab 19). 39 Dr. Gershwin noted that “[o]ver two-thirds of patients with GBS refer symptoms of respiratory or digestive infections within [six] weeks of onset.” Id. He then identified at least 40 infectious organisms thought capable of triggering GBS, most notably, C. jejuni. Id. at 10. C. jejuni, for example, expresses molecules with ganglioside-like structures that induce antibodies, which then go on to attack host gangliosides on neurons, causing GBS. Id. Dr. Whitton highlighted the absence of S. pneumoniae from Dr. Gershwin’s list. Id.

The difference between these bacteria capable of triggering GBS and S. pneumoniae, according to Dr. Whitton, is the composition of the bacterial cell wall. Resp’t’s Ex. C at 11. Bacteria with a thin wall, or gram-negative, are “surrounded by an outer membrane, in the surface of which are embedded the molecules that are thought to be involved in GBS.” Id. This is the ganglioside-like material that cross-reacts with host neuron cells. Id. Conversely, S. pneumoniae is gram positive with a thick cellular wall. Id. “It has a very thick capsule, composed mainly of the polysaccharides that are used in the Prevnar 13 vaccine. S. pneumoniae does not have an outer membrane, and it does not express the molecules that are thought to trigger GBS.” Id.

The cross-reactivity that Dr. Steinman asserted in this case is between phosphoglycerol + polysaccharide in the vaccine and phosphoglycerol that is present in phospholipids within the host myelin sheath. Resp’t’s Ex. C at 21. Dr. Whitton began by noting that Dr. Steinman asserted this theory based on MS studies. Id. Dr. Whitton argued that this is “not appropriate” to use as a model for GBS because the diseases differ in their pathogenesis as evidenced by their different treatment regimens. Id. Differences notwithstanding, Dr. Whitton acknowledged that antiphospholipid antibodies are present in some cases of GBS. Id. at 22. However, “as [he has] consistently opined, autoantibodies (i) may be the cause of disease, (ii) may be the result of the disease; or (iii) may be irrelevant to the disease.” Id. In support of this contention, Dr. Whitton quoted the Nakos et al. paper relied on by Steinman: “It is not well understood whether these anti-phospholipid antibodies play a role in the pathogenesis of the polyneuropathy or represent a part of a more extensive immunoreaction that takes place in the GBS.” Id. (citing Pet’r’s Ex. 55 at 6). He also referred to Gilburd et al., 40 a 1993 study of “the reactivity of GBS sera with various phospholipids which are known to be important constituents of myelin, and serve as autoantigens in other autoimmune conditions.” Resp’t’s Ex. C, Tab 26 at 1. “[O]ur results do not show a significant increase in any specific antiphospholipid antibody. . . . However, some patients [] produce a variety of antiphospholipid . . . antibodies, probably as a result of the myelin damage or as a result of cross reaction with other anti-myelin antibodies.” Id. at 5.

Next, Dr. Whitton discussed the difference between polysaccharides and phospholipids. Resp’t’s Ex. C at 23. Citing Hughes et al., 41 Dr. Whitton noted that the discussion of GBS pathogenesis is always in the context of gangliosides and not phospholipids. Id. (citing Resp’t’s Ex. C, Tab 27). He asserted that the word phospholipid is not mentioned at all. Id. “[T]here is no

39 Anil K. Jasti et al., Guillain-Barré Syndrome: Causes, Immunopathogenic Mechanisms and Treatment, 12 EXPERT REV. CLINICAL IMMUNOLOGY 1175 (2016). 40 B. Gilburd et al., Autoantibodies to Phospholipids and Brain Extract in Patients With the Guillain- Barre Syndrome: Cross-Reactive or Pathogenic?, 16 AUTOIMMUNITY 23 (1993). 41 Richard A. C. Hughes et al., Guillain-Barré Syndrome in the 100 Years Since Its Description by Guillain, Barré, and Strohl, 139 BRAIN 3041 (2016). 15 credible reason to believe that the antibodies described in Bryson [et al.], which recognize a phosphoglycerol + 23F polysaccharide epitope, could also recognize a very different structure, comprising phosphoglycerol remnant + lipid.” Id. Furthermore, Dr. Whitton asserted that Dr. Steinman shifted from a phosphoglycerol target to phosphocholine, the polar head group on the phospholipid phosphatidyl choline. Resp’t’s Ex. C at 24. He argued that “[t]he phosphocholine head group is, chemically, very different from phosphoglycerol.” Id. Dr. Whitton continued, explaining that Ho et al., co-authored by Dr. Steinman, “do[es] not even mention phosphoglycerol or glycerophosphate.” Id. Dr. Whitton questioned that if the phosphate group that exists in phospholipids is the sole target of these phosphate-specific antibodies, what about the other identical phospholipids “present on the membrane of essentially every cell in our body.” Id. at 26.

Even more problematic, according to Dr. Whitton, is his contention that “[t]he phospholipids that are the alleged target of autoantibody attack do not contain phosphoglycerol.” Resp’t’s Ex. C at 28. Instead, the relevant phospholipids (in which phosphoglycerol is used as a building block) are incorporated in larger glycerophospholipids to become the targets that Dr. Steinman described. Id. Dr. Whitton explained that it is similar to comparing the raw ingredients for a baked good to a completed cake, wherein flour, sugar, butter, and eggs “become involved in complex chemical interactions, which change their chemical structure.” Id.

Many free phosphoglycerol molecules exist inside a cell, and some will be exploited when assembling molecules such as glycerophospholipids. But when a free phosphoglycerol molecule moves through this biochemical assembly-line, it is irreversibly altered; it is no longer phosphoglycerol.

Id. Dr. Whitton continued to stress the importance of precise terminology. Resp’t’s Ex. C at 29. He asserted that “when a phosphoglycerol (or glycerophosphate) molecule is used … to build a glycerophospholipid, that molecule is consumed [ ]: (i) it loses both of its hydroxy groups, which (ii) are replaced by very different molecules, called long-chain fatty acids.” Id. He cautioned that “the three carbons remain as part of the glycerophospholipid and, given their origin, those carbons are often referred to as the “glycerol backbone” of the phospholipid.” Id. However, “this nomenclature is ‘misleading,’” and “very different from the starting brick, phosphoglycerol/glycerophosphate.” Id. Dr. Whitton provided diagrams for phosphoglycerol and glycerophosphate. Id.at 26.

16 Resp’t’s Ex. C at 26, Figure 3.

Dr. Whitton argued that Dr. Steinman’s theory depends on “the alleged antibody response induced by a phosphoglycerol + polysaccharide epitope [that] must recognize (cross-react with) a very different proposed epitope that comprises phosphoglycerol + lipid that, he speculates, exists in specific host phospholipids,” such as phosphatidyl-choline. Resp’t’s Ex. C at 30.

Resp’t’s Ex. C at 30, Figure 4.

He then used figures from Dr. Steinman’s report to illustrate these two epitopes. Resp’t’s Ex. C. at 31. “The point being made here is []: regardless of what term you employ, be it phosphoglycerol or glycerophosphate, neither of those chemical compounds is present, intact, in the phospholipids; only vestiges remain.” Id. Dr. Whitton agreed with Dr. Steinman’s referral to Chang et al. that “chemically modifying the phosphoglycerol side chain of the 18C polysaccharide abrogates that polysaccharide’s immunogenicity.” Id. Therefore, he argued that it is unreasonable that the phosphoglycerol remnant in

17 phosphatidyl choline (for example) “must have the same antigenicity as the (relatively intact) phosphoglycerol that is present in a few of the S. pneumoniae polysaccharides.” Id.

Even when comparing phospholipids where the phosphoglycerol remnants are “identical,” Dr. Whitton questioned why there are some that Dr. Steinman labeled reactive, or recognized by the antiphospholipid antibodies, and nonreactive, which are not. Resp’t’s Ex. C at 32.

Dr. Whitton generally restated Dr. Steinman’s second theory of causation “that antibody responses against the CRM197 protein can cause GBS.” Resp’t’s Ex. C at 8. He noted that Dr. Steinman’s conclusions are based largely from a layered homology analysis using BLAST searches. Id. Immediately, Dr. Whitton stated that “whenever two average-length proteins are properly compared, short homologies will inevitably be found.” Id. at 36. Indeed, these homologies are “commonplace,” and of little importance. Id. Dr. Whitton referred to the 2006 Silvanovich et al. 42 paper that sought “to assess whether or not short peptide matches were valuable in predicting whether or not a protein was allergenic.” Id. at 38 (citing Resp’t’s Ex C, Tab 30). The paper’s abstract ended with the statement that “searches for short amino acid sequence matches of eight amino acids or fewer to identify proteins as potential cross-reactive allergens is a product of chance and adds little value to allergy assessments for newly expressed proteins.” Resp’t’s Ex. C, Tab 30 at 1. Dr. Whitton asserted that due to the number of short homologies between two proteins of average length, cross-reactivity can be asserted with respect to any host target. Resp’t’s Ex. C at 39.

Thus, regardless of the disease from which a petitioner suffers, Dr. Steinman will always be able to identify short homologies between a disease-related host protein, and a protein in the relevant vaccine. It works in the other direction, too: not only can Dr. Steinman select the host protein that best fits the petitioner’s alleged disease, he also can apply his approach to any vaccine; he will always be able to find homologies. So, if a petitioner has received Prevnar 13 then, irrespective of the alleged disease (be it GBS, narcolepsy, transverse myelitis, or whatever), a proper comparison of CRM197 against a chosen host protein will always find homologies. In other words, Dr. Steinman’s BLAST approach will always achieve his desired outcome; he will identify homologies regardless of the alleged disease, and regardless of the vaccine that he claims caused it.

In the present case, Dr. Whitton explained that the polysaccharides from the 13 serotypes found in Prevnar 13 are individually cross-linked to CRM197, “a mutated variant of diphtheria toxin.” Resp’t’s Ex. C at 6–7. He clarified, “CRM197 is not “used to conjugate the pneumococcal polysaccharides in Prevnar 13 to an immunogenic protein carrier, [as Dr. Steinman alleged, but rather], CRM197 is the immunogenic protein carrier.” Id. at 40. Dr. Whitton then analyzed the BLAST results from CRM197 and contactin-1. Id. He relied on the 2006 Silvanovich et al. approach because “this is the only approved use of BLAST for identifying protein sequences of possible immunological relevance.” Id. at 42. The two criteria both must be met or exceeded for 42 Andre Silvanovich et al., The Value of Short Amino Acid Sequence Matches for Prediction of Protein Allergenicity, 90 TOXICOLOGICAL SCI. 252 (2006). 18 possible immunological relevance for an identified homology. Id. “[F]irst, the length of the homology must be at least 80 amino acids; and, second, after the sequences are aligned, at least 28 of the 80 amino acids (28/80 = 35%) must be identical.” Id. These criteria can be applied to linear antibody epitopes or discontinuous, but following identification, there is a “very stringent criteria [that is applied] before claiming to have identified a potentially immunologically relevant sequence.” Id. at 43.

Dr. Whitton identified the Expect (“E”) value as “a parameter that describes the number of hits one can ‘expect’ to see by chance when searching a database of a particular size.” Resp’t’s Ex. C at 43. He then asked, what is a possible meaningful E value for immunologically significant homologies? Id. at 44. According to Dr. Whitton, Silvanovich et al. answered that question: below 3.9 x 10-7. Id. The 2009 Silvanovich et al. 43 paper identified the threshold for identifying potential allergenic cross-reactivity of transgene encoded proteins in genetically enhanced crops when using BLAST searches. Resp’t’s Ex. C, Tab 32 at 1. A threshold of 3.9E-07 “has a potential false positive rate as high as 95% for the identification of known allergens. Yet, it is of sufficient sensitivity that it will discriminate against the majority of alignments that [exhibit] protein composition bias.” Id. at 5.

Of the four homologies that Dr. Steinman identified, Dr. Whitton focused on the homology noted between the CRM197 sequence WEQAKALSVE and the contactin-1 sequence WDHVVALSNE. Resp’t’s Ex. C at 45. Dr. Whitton noted that the sequences compared were longer in order to argue that the results are cherry picked. Id.

Id. (citing Pet’r’s Ex. 42 at 31).

Next. Dr. Whitton attacked Dr. Steinman’s “assum[ption] that any immune response that recognizes WEQAKALSVE must also recognize WDHVVALSNE.” Resp’t’s Ex. C at 46. Because these sequences and the identified homology does not meet any of the three Silvanovich et al. criteria, Dr. Whitton argued that there is no evidence that this homology occurs for any reason other than by chance. Id. Dr. Whitton argued further that Dr. Steinman’s filter funnel does not provide evidence of immunogenicity. Id. at 50. First, Dr. Whitton argued that the CRM107 sequence, “WEQAKALSVE[,] is not a known epitope” identified in the IEDB. Id. Dr. Steinman associated this sequence to the IEDB “by changing the default setting, Exact Match, to a lower- stringency search, termed ‘BLAST Option: 70%.’” Id. at 50 (citing Pet’r’s Ex. 42 at 35). Dr. Whitton identified this sequence within the database as a part of a larger, 20-amino-acid-long sequence that “could activate some human CD4+ T cells.” Id. at 52. He added that “we do not know what part of the 20 amino acid long [sequence] is responsible for activating the T cells.” Id. at 51. Additionally, the contactin-1 sequence, WDHVVALSNE, “returned no hits, even when carried out using the low-stringency BLAST approach.” Id. Therefore, “there is no evidence that the alleged target sequence in contactin-1, WDHVVALSNE, is recognized by the human immune system.” Id. Dr. Whitton continued that even if these two chains were molecular mimics, Dr.

Andre Silvanovich et al., The Use of E-Scores to Determine the Quality of Protein Alignments, 54 43

REGULATORY TOXICOLOGY & PHARMACOLOGY 26 (2009). 19 Steinman would still need to “show that both peptides can be recognized by the same antibody or by the same T cell.” Id.

Although Dr. Whitton disagreed with Dr. Steinman’s assertion that that WEQAKALSVE within contactin-1 is immunogenic, he conducted a BLAST search to identify “better homologies in many other human proteins because . . . those other human proteins – and the tissues that express them – should be the target of autoimmune assault by the CRM197-induced antibodies.” Resp’t’s Ex. C at 54. He noted that “thousands of proteins were identified” but “contactin was not among [them].” Id. at 54–55. As a control, Dr. Whitton ran a search of the WDHVVALSNE peptide sequence and “contactin-1 was at the top, with an E-value of 3 x 10-4.” Id. at 55. Dr. Whitton argued that this result is evidence that BLAST searches do work to identify homology, “if they exist.” Id. “This validates [Dr. Whitton’s] conclusion regarding the WEQAKALSVE-based BLAST search; no homology with contactin-1 was found, indicating that no meaningful homology exists.” Id. Dr. Whitton reiterated that “Dr. Steinman’s BLAST search did not identify [WEQAKALSVE], Dr. Steinman’s BLAST search identified an 18 amino-acid long peptide as being partially homologous with contactin-1. Dr. Steinman then cherry-picked the shorter sequence” contained within. Id.

Dr. Whitton conceded “that short peptides can, occasionally, be involved in molecular mimicry.” Resp’t’s Ex. C at 58. However, he attacked Dr. Steinman’s use of literature, some of which is self-authored, to support molecular mimicry as a mechanism for Prevnar 13 vaccine- caused GBS. Id. First, Dr. Whitton asserted that Dr. Steinman overstated the conclusion in Lanz et al. Id. (citing Pet’r’s Ex. 67). Evidence that “some individuals with MS have antibodies that can cross-react with both EBNA-1 and GlialCAM . . . most certainly does not demonstrate that this cross-reactivity causes MS!” Id. He quoted the conclusion of the paper, which stated that “[o]ur results provide a mechanistic link for the association between MS and EBV, and could guide the development of novel MS therapies.” Id.

Second, Dr. Whitton stressed that many of the studies, including Lanz et al., are related to EBV and MS, neither of which are present in this case. Id. He described the Bjornevik et al. 44 as “tour de force of epidemiology, involving ~10 million people and carried out over ~20 years[ that] appear[s] to have demonstrated that [MS] is caused by EBV.” Id. at 57 (citing Resp’t’s Ex. C, Tab 33). He continued that EBV is a live virus, compared to Prevnar 13, a non-live vaccine against a bacterium; and MS is a different disease characterized by differences in diagnostic criteria, duration, and treatment. Id. at 58.

The end of Dr. Whitton’s report is a summary of criticisms of Dr. Steinman’s arguments and restatements of some of his asserted inconsistencies in Dr. Steinman’s theories. Resp’t’s Ex. C at 63. He noted generally, that despite Dr. Steinman’s heavy reliance on molecular mimicry as a mechanism for GBS by comparison to MS, his own article “make[s] no mention whatsoever of phosphoglycerol or phospholipids as possible targets of autoimmune attack causing MS.” Id. at 62.

44 Kjetil Bjornevik et al., Longitudinal Analysis Reveals High Prevalence of Epstein-Barr Virus Associated with Multiple Sclerosis, 375 SCIENCE 296 (2022). 20 c. Dr. Steinman’s Supplemental Report

Dr. Steinman responded directly to Dr. Whitton’s report starting with the conclusion from his own professional experience that molecular mimics can cause “widespread unwanted immune reactions” and “provoke neuroinflammatory disease” in humans. Pet’r’s Ex. 85 at 4. Next, Dr. Steinman explained that “the components of the entire [S. pneumoniae] bacterium contain various proteins, sugars and lipids which serve to subvert the human immune system.” Id. at 4–5. He clarified that his cross-reactivity theory is based on the fact that the sugars in Prevnar 13 are combined with CRM197 and formulated with alum. Id. These additions, according to Dr. Steinman, were deemed “necessary to get adequate immunity to the sugars.” Id. Furthermore, they distinguish the infection from the vaccine in a way that explains the latter’s cross-reactivity. Id. This cross-reactivity, Dr. Steinman maintained, occurs because “the antibody binds to the phosphoglycerol moiety of the sugar as well as to the sugars” in the 23F and 18C components of Prevnar 13 that “is also central to the composition of the phospholipids in myelin.” Id. at 5–6. He argued that Ho et al. established “a strong attraction for binding to these phosphate moiety, independent of what is attached to it.” Id. at 6. Dr. Steinman also cited to Barbar et al. 45 to assert “that binding to the phosphate group was retained, no matter what the structure was that was attached to it.” Id. (citing Pet’r’s Ex. 88).

The Barbar et al. article began by stating that “current procedures to produce hapten-carrier protein conjugates . . . disallow[] determination of specific structural details of antigen-antibody interactions.” Pet’r’s Ex. 88 at 1. The authors “sought to analyze the carrier contribution to hapten binding by utilizing small, homogeneous amino acid-hapten conjugates.” Id. They noted at the outset that “[t]he hapten phosphocholine is immunogenic when coupled to protein carriers.” Id. Building from that, Barbar et al. “synthesized a series of haptenated carriers made from amino acids and peptides,” and found that “[t]he affinity for hapten was shown to be modulated by the identity of the carrier molecule.” Id. at 2. Additionally, “[t]he bound confirmations of at least some of the carriers were found to be influenced by antibody.” Id. The authors concluded “that binding involves specific interactions that change the conformation of both the hapten and antibody. . . . Thus there is a conformational distortion of the carrier as well.” Id. at 9. They noted that “conformational mobility of the antibody combining site has been proposed as a possible mechanism for cross-reactivity.” Id. at 10. Barbar et al. also suggested that this “mechanism may be common.” Id. Ultimately, “the differences in I50[46] values and binding affinities of the hapten when coupled to various small carriers are not attributable to changes in the orientation of the hapten in the combining site, but rather to interactions with the carrier.” Id. Dr. Steinman analogized binding of a phosphate group to the hook on an aircraft carrier attaching to a fighter jet. Pet’r’s Ex. 85 at 8.

Upon landing, there is contact of the wheels under the nose of the plane and under the wings with the deck. However, the primary binding is to the arresting hook on the deck of the carrier: “A tailhook, arresting hook, or arrester hook is a device attached to the empennage (rear) of some military fixed-wing aircraft. The hook is

45 Elisar Barbar et al., Binding of Phenylphosphocholine–Carrier Conjugates to the Combining Site of Antibodies Maintains a Confirmation of the Hapten, 35 BIOCHEMISTRY 2958 (1996). 46 I50 values correspond to the hapten concentration needed to inhibit 50% of the antibody binding to phosphocholine-histone. See Pet’r’s Ex. 80 at 3 (Sven Jarius et al., Neuromyelitis Optica, 6 NATURE REVIEWS 85 (2020)). 21 used to achieve rapid deceleration during routine landings aboard aircraft carrier flight decks at sea.”

Id. The hook, “all important in landing the plane and keeping it on deck,” is analogous to the phosphate group. Id. Dr. Steinman opined that the autoantibodies targeting the phosphate groups in MS “is exceptionally close to what [] would constitute certainty on the question of whether humans who receive a pneumococcal vaccine make antibodies that target phosphoglycerol.” Id. at 8.

Next, Dr. Steinman directly addressed Dr. Whitton’s contention that the Ho et al. article does not mention phosphoglycerol or glycerophosphate. Pet’r’s Ex. 82 at 8. “Similarities are seen with binding to phospholipids in myelin in the Ho et al. paper.” Id. Ho et al. was an analytical study done to “discover[] autoimmune targets and developing therapeutic strategies for MS.” Pet’r’s Ex. 51 at 1. To determine whether the autoantibody targeted lipids have a role in autoimmune demyelination, the authors tested the effect of select lipids on EAE, a mouse model of MS. Id. at 2. The lipids selected included myelin lipids (gangliosides), membrane lipids (phosphatidylcholine), microbial lipids (lipopolysaccharide), and oxidized lipids (1-palmitoyl2- glutaroyl-sn-glycero-3-phosphocholine (“PGPC”) and its derivatives). Id. Dorland’s Online Dictionary provides definitions for three of the four subgroups. First, ganglioside is defined as “any of a group of [glycolipids] in which the polar head group on ceramide is a sialic acid– containing oligosaccharide linked via a glucose residue; they occur predominantly in tissues of the central nervous system.” Ganglioside, DORLAND’S. Glycolipids contain carbohydrates and the term “is used almost exclusively to denote the lack of a phosphate group.” Glycolipid, DORLAND’S. Second, phosphatidylcholine is “a phospholipid in which choline is attached to the phosphate group of phosphatidic acid by an ester linkage; it is a major component of cell membranes and is localized preferentially in the outer surface of the plasma membrane.” Phosphatidylcholine, DORLAND’S. Phospholipids are further defined as “the major form of lipid in all cell membranes.” Phospholipid, DORLAND’S. Third, a lipopolysaccharide is “a complex of lipid and polysaccharide” that is “a major component of the cell wall of gram-negative bacteria.” Lipopolysaccharide, DORLAND’S. The fourth type of lipid studied by Ho et al., PGPC is defined by the authors as “a derivative of oxidized phosphatidylcholine.” Pet’r’s Ex. 51 at 3. The authors were particularly interested in PGPC “because antibodies for oxidized phosphatidylcholine are present in MS brain lesions.” Id. Additionally, “unlike the other lipids tested, PGPC attenuated the development of EAE and ameliorated EAE after onset. A reduction in T cell activation, a process important in MS pathogenesis, accompanied the PGPC-induced attenuation of EAE.” Id. These findings caused the authors to investigate “autoantibody targeting of seven lipids that have a glycero-3-phosphocholine backbone in common with PGPC, as well as targeting of other structurally similar lipids . . . including a phosphate head group with one or two nonpolar side chains.” Id. Of the seven, three glycerol-3-phosphocholine–containing lipids exhibited autoantibody reactivity during microarray analysis. Id. The authors hypothesized “that autoantibodies present in [relapse-remitting MS patient] CSF target the phospholipids’ phosphate head group and that the affinity of antibody-lipid binding is not specific to a particular phospholipid.” Id. Further support of this idea is evidenced by autoantibodies not targeting myelin lipids without the phosphate polar head. Id. The authors noted that the “binding of [relapse-remitting MS] CSF autoantibodies to these lipids is dependent on the presence of (i) a nonbulky polar head group such as a phosphate group and (ii) at least one long hydrocarbon side chain.” Id. Ultimately, “[w]hereas the polar head groups are the lipid

22 components targeted by the autoantibodies, the fatty acid side chains are the components that mediate the lipids’ anti-inflammatory effects.” Id. at 9.

The discussion section of the Ho et al. article posed several suggestions about the pathogenesis of MS based on the studies of these autoantibodies. Pet’r’s Ex. 51 at 9. Notably that “[t]he destruction of myelin involves anti-lipid autoantibodies, which can induce demyelination and prevent remyelination in mouse models of MS.” Id. Additionally, the results of this study suggest that “the antibodies to oxidized phosphatidylcholine derivatives that we detect in CSF [are generated as part of the pathological process of autoimmune demyelination and] can bind their lipid targets in MS brain.” Id. Dr. Steinman then asserted that the phospholipids in the myelin of MS patients discussed in Ho et al. “are identical in many cases to the phospholipids” in Nakos et al. Pet’r’s Ex. 85 at 9. He noted that Al-Temeemi et al. 47 “[m]easur[ed] immunoglobulin G and immunoglobulin M antiphospholipid antibodies of incidental untreated GBS patients and compar[ed] them with that of normal population.” Id. at 14 (citing Pet’r’s Ex. 89). He noted the authors’ findings that “GBS cases have statistically significant higher [immunoglobulin M antiphospholipid antibodies] titers during the first week and the first two weeks of illness than healthy controls, and [antiphospholipid antibodies] may have a protective effect in GBS.” Id. (citing Pet’r’s Ex. 89). Nakos et al. also suggested “that antibody mediated injury is a predominant disorder in the demyelinating form of GBS.” Pet’r’s Ex. 55 at 6–7. They described GBS pathology as an “extensive immune reaction” that “is directed against components of Schwann cell[48] membrane and is accompanied by the characteristic feature of vesicular demyelination.” Id. at 7. In conclusion, they asserted that “it is crucial to investigate how anti-phospholipid antibodies are related to specific antigens in Schwann cell membrane.” Id. Dr. Steinman strongly disagreed with Dr. Whitton’s opinion of the significance of Nakos et al., explaining that he “think[s] that Dr. Whitton is reading the Nakos paper rather selectively. But that is why two experts debate these details.” Pet’r’s Ex. 85 at 14.

Returning to Ho et al., Dr. Steinman directly challenged Dr. Whitton’s contention that his article did not mention phosphoglycerol or glycerophosphate. Pet’r’s Ex. 85 at 15. He reproduced Figure 2C, depicting “antibody reactivity to various glycerol-3-phosphocholine lipids in CSF samples from patients with [relapsing remitting] MS and from control patients with [other noninflammatory, neurological disease].” Id. (citing Pet’r’s 51 at 4). Dr. Steinman asserted that “panel C speaks in English to the actual chemical structures shown in this sound and reliable paper. We have …Glycero-3[phospho…] repeated in English in six lines in a row.” Id. Noting that he was a co-author, Dr. Steinman wrote, “[w]e found autoantibodies in MS target a phosphate group in phosphatidylserine and oxidized phosphatidylcholine derivatives.” Id. Indeed, Dr. Steinman asserted “the phosphoglycerol backbone is a critical constituent of many of the phospholipids described in Ho et al.,” including the glycerol- 3-phosphoethanolamine and glycerol-3-phosphoL- Serine. Id. at 16. Lastly, as it relates to his phosphoglycerol theory, Dr. Steinman noted that Dr. Whitton’s other critiques were addressed in his initial report. Id.

47 Temeem M. Al-Temeemi et al., Antiphospholipid Antibody in Serum of Guillain-Barre Syndrome Patients, 10 IRAQI J. MED. SCI. 191 (2012). 48 Schwann cells are “any of the large nucleated cells whose cell membrane spirally enwraps the axons of myelinated peripheral neurons and is the source of myelin; a single Schwann cell supplies the myelin sheath between two nodes of Ranvier.” Schwann Cell, DORLAND’S. 23 The second part of Dr. Steinman’s responsive report discussed Dr. Whitton’s opinions related to his BLAST search and conclusions. Pet’r’s Ex. 85 at 18. He argued that Dr. Whitton’s criteria are based on “searches over much longer stretches of protein-80 amino acids and does not address the chunks of protein in an immunological epitope.” Id. Dr. Steinman relied on the Raju et al. 49 paper to explain that “the immune system is probed with [shorter] peptides of 10 to 20 amino acids.” Pet’r’s Ex. 85 at 18 (citing Pet’r’s Ex. 74). He also cited the Lanz et al. paper to assert that “peptides of length 10 to 20 amino acids are recognized by the immune system.” Id. (citing Pet’r’s Ex. 67).

In Raju et al., the authors suggested that “[i]dentification of [immunodominant region sequences] might facilitate the design of peptide vaccines for immunoprophylaxis of diphtheria.” Pet’r’s Ex. 74 at 8. Diphtheria toxin (“DTX”) is made up of a single chain of 535 amino acids. Id. at 1. The authors broke that chain “into fragments . . . leading to arrest of protein synthesis.” Id. at 2. They then used these peptide chains “to identify sequence regions recognized by CD4+ cells of seven healthy humans.” Id. The study included fragments of “53 peptides, 20 residues long and overlapping by [ten] residues, corresponding to the complete DTX sequence.” Id. at 2–3. The authors explained this “length was chosen because, although class II-restricted epitopes are only 13-17 residues long the presence of extra residues does not interfere with epitope presentation.” Id. at 3. The authors cautioned that they “do not know which residues within the [immunodominant region sequences] interact with the different class II molecules, and [] cannot identify structural correlates between the sequence of the IRS peptides and their ability to bind to different presenting molecules” Id. at 8. However, “the binding motifs identified for peptide binding to [HLA-]DRl, and different [HLA-]DR4 subtypes are present in most or all the DTX immunodominant region sequences.” Id.

In 2022, Lanz et al. published an article “demonstrat[ing] high-affinity molecular mimicry between the EBV transcription factor EBV nuclear antigen 1 (EBNA1) and the [CNS] protein glial cell adhesion molecule (GlialCAM) and provid[ing] structural and in vivo functional evidence for its relevance.” Pet’r’s Ex. 67 at 1. Monoclonal antibody 50 MS39p2w174 is an immunoglobulin superfamily cell adhesion molecule expressed in the CNS that binds with GlialCAM. Id. at 4. MS39p2w174 also bound to the EBNA1 protein and the EBNA1AA386–405 peptide, but “its binding affinity for the native peptide GlialCAMAA370–389 was three orders of magnitude lower than for GlialCAM protein.” Id. at 5. “MS39p2w174 did not demonstrate high enrichment for any single peptide, which suggests that it has low affinity for multiple native peptides.” Id. at 5.

The 2023 Lanz et al. 51 article was described by the authors as “a roadmap for what may be studied next in understanding how EBV triggers MS.” Pet’r’s Ex. 82 at 3. They believed that their research “may also illuminate parallel mechanisms in other diseases including systemic lupus

49 Raghavanpillai Raju et al., Epitopes for Human CD4+ Cells on Diphtheria Toxin: Structural Features of Sequence Segments Forming Epitopes Recognized by Most Subjects, 25 EUR. J. IMMUNOLOGY 3207 (1995). 50 Monoclonal antibodies are “chemically and immunologically homogenous antibodies produced by hybridomas, used as laboratory reagents in radioimmunoassays, ELISA, and immunofluorescence assays.” Monoclonal Antibody, DORLAND’S. 51 Tobias V. Lanz et al., Roadmap for Understanding Mechanisms on How Epstein-Barr Virus Triggers Multiple Sclerosis and for Translating These Discoveries in Clinical Trials, 23 CLINICAL & TRANSLATIONAL IMMUNOLOGY 1438 (2023). 24 erythematosus, rheumatoid arthritis, Sjogren’s syndrome, Long COVID and even myalgic encephalomyelitis/ chronic fatigue syndrome.” Id. The authors identified the region of the peptide of EBNA-1 between amino acids 365 and 420 that shared homology with GlialCAM. Id. at 4. Within that region, “[c]lonally expanded antibodies isolated from the cerebrospinal fluid of MS patients target EBNA-1 residues 386–405 that cross-react with the CNS cell adhesion molecule GlialCAM and are associated with CD4 and CD8 T cell responses targeting GlialCAM.” Id. The authors focused on “the molecular mechanisms underlying how clonal antibody in the CSF emanates in widespread molecular mimicry to key antigens in the nervous system including GlialCAM, a protein associated with chloride channels.” Id. at 3.

The epitopes, EBNA 1 AA386-405 and GlialCAM AA370-389, consist of 19 amino acids and “show[] that the landing pad for an antibody is a small domain of the protein of 10-20 amino acids.” Pet’r’s Ex. 85 at 19. Dr. Steinman argued that “[t]he mimic, where [five] identical amino acids in a stretch of 12 between EBNA 1 and GlialCAM, also was tested in the EAE model, where it worsened disease.” Id. at 20. He noted that “[i]n some cases alignment is extensive and e-values approach zero.” Id. at 21. To account for this, Dr. Steinman reiterated that the BLAST search is followed by his multi-step, filter funnel to support molecular mimicry once homology has been identified. Id. at 23.

d. Dr. Whitton’s Supplemental Report

Dr. Whitton’s second filed report sought to address Dr. Steinman’s direct responses to the criticisms and concerns that Dr. Whitton detailed in his initial report. Resp’t’s Ex. F at 4. Dr. Whitton asserted that Dr. Steinman has modified one of the identified molecular mimics asserted in this case. Id. Dr. Whitton stated that initially “Dr. Steinman hypothesized that a phosphoglycerol molecule that is attached to some S. pneumoniae polysaccharides in Prevnar 13 can induce antibodies that can cross-react with a phosphoglycerol that is present in phospholipids, and that this results in GBS.” Id. In response to Dr. Steinman’s second report, Dr. Whitton stated that the theory is now based “on recognition of a phosphate residue that just happens to be on a phosphoglycerol molecule (or on a remnant thereof).” Id. Dr. Whitton wrote “if the proposed target is actually phosphate, rather than phosphoglycerol, then I agree that these phospholipids do contain a phosphate moiety.” Id. Consequently, Dr. Whitton did not direct any further attention to whether the phospholipids identified by Dr. Steinman contain intact phosphoglycerol. Id.

Instead, Dr. Whitton noted Dr. Steinman’s reliance on Barbar et al. and criticized his “attempt to convince us that the antibodies can recognize phosphate alone.” Resp’t’s Ex. F at 6. Dr. Whitton made several observations about the substance of the Barbar et al. study. Id. at 7. He noted that “[t]he antibodies [studied by Barbar et al.] are specific for a molecule named phenylphosphocholine, not for phosphate;” and they, along with “the target structures, [] have no relationship to S. pneumoniae polysaccharides.” Id. Additionally, the researchers “do not attempt to induce antibodies using very small molecules; rather, they use synthesized (preexisting) antibodies, and determine what ‘shapes’ those antibodies can recognize.” Id. Dr. Whitton also noted that “even the largest of the materials attached to [phenylphosphocholine] is far smaller than the bacterial polysaccharides to which the phosphate groups are linked in some S. pneumoniae polysaccharides.” Id.

25 Expanding on Dr. Steinman’s use of a fighter jet analogy, Dr. Whitton countered with his own interpretation: “in allowing the plane to land, the carrier does not rely solely on the interaction between the wire rope and the arresting hook.” Resp’t’s Ex. F at 8. He explained:

In summary, the carrier’s deck (the Bryson antibody) captures the plane (the phosphate + 23F polysaccharide epitope) when (i) the wire rope grabs the arresting hook (the phosphate moiety) and (ii) the rest of the deck accepts the plane’s wheels (the eight points of contact with S. pneumoniae sugars).

Id. Because each epitope has a different polysaccharide, “the fighter with ‘18C wheels’ can land only on the aircraft carrier (antibody) that can accept those wheels.” Id. Dr. Whitton argued that this makes his point that the hook is not a sufficient point of recognition because “even though the 23F deck has a wire rope to accept the fighter’s arresting hook, that deck does not have the correct surface configuration to capture the 18C fighter’s wheels.” Id.

Dr. Whitton next clarified the significance of linear versus discontinuous chains of amino acids. Resp’t’s Ex. F at 14. He argued that in order for most amino acid chains “to achieve biological activity, [they] must fold up into a 3D structure.” Id. Dr. Whitton noted that a folded protein can contain a linear epitope, but most epitopes are discontinuous, i.e., made from shorter chains of amino acids that are “scattered” throughout a longer sequence and “brought together by protein folding.” Id. Each antibody epitope is made up of amino acids sequences present along the “surface of the protein; many other amino acids are buried in the middle of the structure and . . . invisible to antibodies.” Id. Dr. Whitton opined that the short homologies identified by Dr. Steinman’s BLAST searches are too short to “contain an antibody epitope because the great majority of antibody epitopes are discontinuous, and span lengths far longer than 10-12 amino acids.” Id. In the cases that Dr. Steinman does provide examples of short homologies, such as the one identified in the Fujinami & Oldstone52 paper, the amino acid sequence from myelin basic protein (“MBP”) “was already known to be a molecular mimic, and was already known to cause disease (EAE).” Id. at 18 (citing Pet’r’s Ex. 76). That sequence was then used to find homology in viral protein. Id. at 19. The corresponding sequence “was found in hepatitis B virus polymerase (HBVP); . . . and it shares [six] identical amino acids with the MBP.” Id. Dr. Whitton argued that this type of comparison is “completely different” and only “similar because they both use a computer search.” Id.

V. Applicable Legal Standards

To receive compensation under the Vaccine Act, a petitioner must demonstrate either that: (1) the petitioner suffered a “Table injury” by receiving a covered vaccine and subsequently developing a listed injury within the timeframe prescribed by the Vaccine Injury Table set forth at 42 U.S.C. § 300aa-14, as modified by 42 C.F.R. § 100.3; or (2) that the petitioner suffered an “off- Table injury,” one not listed on the Table, as a result of him receiving a covered vaccine. See § 11(c)(1)(C); Moberly v. Sec’y of Health & Hum. Servs., 592 F.3d 1315, 1321 (Fed. Cir. 2010); Capizzano v. Sec’y of Health & Hum. Servs., 440 F.3d 1317, 1319–20 (Fed. Cir. 2006). In this case, GBS is not a Table injury associated with the Prevnar 13 vaccine, and thus Petitioner must prove by preponderant evidence that his injury was caused-in-fact by a Table vaccine.

52 Robert S. Fujinami & Michael B. A. Oldstone, Amino Acid Homology Between the Encephalitogenic Site of Myelin Basic Protein and Virus: Mechanism for Autoimmunity, 230 SCIENCE 1044 (1985). 26 A. Factual Issues A petitioner must prove, by a preponderance of the evidence, the factual circumstances surrounding his claim. § 13(a)(1)(A). To resolve factual issues, the special master must weigh the evidence presented, which may include contemporaneous medical records and testimony. See Burns v. Sec’y of Health & Hum. Servs., 3 F.3d 415, 417 (Fed. Cir. 1993) (explaining that a special master must decide what weight to give evidence including oral testimony and contemporaneous medical records). Contemporaneous medical records, “in general, warrant consideration as trustworthy evidence.” Cucuras v. Sec’y of Health & Hum. Servs., 993 F.2d 1525, 1528 (Fed. Cir. 1993); but see Kirby v. Sec’y of Health & Hum. Servs., 997 F.3d 1378, 1382 (Fed. Cir. 2021) (rejection the presumption that “medical records are accurate and complete as to all the patient’s physical conditions”); Shapiro v. Sec’y of Health & Hum. Servs., 101 Fed. Cl. 532, 538 (2001) (“[T]he absence of a reference to a condition or circumstance is much less significant than a reference which negates the existence of the condition or circumstance.”).

B. Causation-In-Fact

To establish causation-in-fact, a petitioner must demonstrate by a preponderance of the evidence that the vaccine was the cause of the injury. § 13(a)(1)(A). A petitioner is required to prove that the vaccine was “not only a but-for cause of the injury but also a substantial factor in bringing about the injury.” Moberly, 592 F.3d at 1321–22 (quoting Shyface v. Sec’y of Health & Hum. Servs., 165 F.3d 1344, 1352–53 (Fed. Cir. 1999).

In the seminal case of Althen v. Sec’y of Health & Hum. Servs., the Federal Circuit set forth a three-pronged test used to determine whether a petitioner has established a causal link between a vaccine and the claimed injury. See 418 F.3d 1274, 1278–79 (Fed. Cir. 2005). The Althen test requires petitioners to set forth: “(1) a medical theory causally connecting the vaccination and the injury; (2) a logical sequence of cause and effect showing that the vaccination was the reason for the injury; and (3) a showing of a proximate temporal relationship between vaccination and injury.” Id. at 1278. To establish entitlement to compensation under the Program, a petitioner is required to establish each of the three prongs of Althen by a preponderance of the evidence. Id. “[C]lose calls regarding causation are resolved in favor of injured claimants.” Id. at 1280. Further, evidence used to satisfy one prong of the test may overlap to satisfy another prong. Capizzano, 440 F.3d at 1326.

Under the first prong of Althen, a petitioner must offer a scientific or medical theory that answers in the affirmative the question: “can the vaccine[] at issue cause the type of injury alleged?” See Pafford v. Sec’y of Health & Hum. Servs., No. 01-0165V, 2004 WL 1717359, at *4 (Fed. Cl. Spec. Mstr. July 16, 2004), mot. for rev. den’d, 64 Fed. Cl. 19 (2005), aff’d, 451 F.3d 1352 (Fed. Cir. 2006). To satisfy this prong, a petitioner’s theory must be based on a “sound and reliable medical or scientific explanation.” Knudsen v. Sec’y of Health & Hum. Servs., 35 F.3d 543, 548 (Fed. Cir. 1994). Such theory must only be “legally probable, not medically or scientifically certain.” Id. at 548–49. Petitioners are not required to identify “specific biological mechanisms” to establish causation, nor are they required to present “epidemiologic studies, rechallenge[] the presence of pathological markers or genetic disposition, or general acceptance in the scientific or medical communities.” Capizzano, 440 F.3d at 1325 (quoting Althen, 418 F.3d at 1280). Scientific and “objective confirmation” of the medical theory with additional medical documentation is unnecessary. Althen, 418 F.3d at 1278–81; see also Moberly, 592 F.3d at 1322. However, as the Federal Circuit has made clear, “simply identifying a ‘plausible’ theory of 27 causation is insufficient for a petitioner to meet her burden of proof.” LaLonde v. Sec’y of Health & Hum. Servs., 746 F.3d 1334, 1339 (Fed. Cir. 2014) (citing Moberly, 592 F.3d at 1322). Indeed, the Federal Circuit has “consistently rejected theories that the vaccine only ‘likely caused’ the injury and reiterated that a ‘plausible’ or ‘possible’ causal theory does not satisfy the standard.” Boatmon v. Sec’y of Health & Hum. Servs., 941 F.3d 1351, 1360 (Fed. Cir. 2019) (citing Moberly, 592 F.3d at 1322; LaLonde, 746 F.3d at 1339); see also Cerrone v. Sec’y of Health & Hum. Servs., 146 F.4th 1113, 1121 (Fed. Cir. 2025) (explaining that “simply identifying a plausible theory of causation is insufficient for a petitioner to meet her burden of proof.” (internal quotes omitted)). Rather, “[a] petitioner must provide a reputable medical or scientific explanation that pertains specifically to the petitioner’s case.” Moberly, 592 F.3d at 1322. In general, “the statutory standard of preponderance of the evidence requires a petitioner to demonstrate that the vaccine more likely than not caused the condition alleged.” LaLonde, 746 F.3d at 1339.

Furthermore, establishing a sound and reliable medical theory connecting the vaccine to the injury often requires a petitioner to present expert testimony in support of his claim. Lampe v. Sec’y of Health & Hum. Servs., 219 F.3d 1357, 1361 (Fed. Cir. 2000). The Supreme Court’s opinion in Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579 (1993) requires that courts determine the reliability of an expert opinion before it may be considered as evidence. However, in the Vaccine Program, the Daubert factors are used in the weighing of the reliability of scientific evidence proffered. Davis v. Sec’y of Health & Hum. Servs., 94 Fed. Cl. 53, 66–67 (2010) (“[U]niquely in this Circuit, the Daubert factors have been employed also as an acceptable evidentiary-gauging tool with respect to the persuasiveness of expert testimony already admitted.”); see also Cedillo v. Sec’y of health & Hum. Servs., 617 F.3d 1328, 1339 (Fed. Cir. 2010) (citing Terran v. Sec’y of Health & Hum. Servs., 195 F.3d 1302, 1316 (Fed. Cir. 1999)). It is also not required that special masters utilize Daubert when weighing the reliability of expert testimony. See Boatmon, 941 F.3d at 1359 (“Special masters may, but are not required to, analyze expert testimony according to Daubert.” (emphasis in original)). Under Daubert, the

Factors for analyzing the reliability of testimony are: (1) whether a theory or technique can be (and has been) tested; (2) whether the theory or technique has been subjected to peer review and publication; (3) whether there is a known or potential rate of error and whether there are standards for controlling the error; and (4) whether the theory or technique enjoys general acceptance within a relevant scientific community.

Terran, 195 F.3d at 1316 n.2 (citing Daubert, 509 U.S. at 592–95).

The Daubert factors are “meant to be helpful, not definitive.” Kumho Tire Co. v. Carmichael, 526 U.S. 137, 151 (1999). The factors do not “constitute a ‘definitive checklist or test’” and may be applied differently depending on the facts of a particular case. Id. at 150 (quoting Daubert, 509 U.S. at 593).

“In short, the requirement that an expert’s testimony pertain to ‘scientific knowledge’ establish a standard of evidentiary reliability.” Daubert, 509 U.S. at 590 (citation omitted). Thus, for Vaccine Act claims, a “special master is entitled to require some indicia of reliability to support the assertion of the expert witness.” Moberly, 592 F.3d at 1324. Nothing requires the acceptance of an expert’s conclusion “connected to existing data only by the ipse dixit of the expert,” especially if “there is simply too great an analytical gap between the data and the opinion proffered.” Synder v. Sec’y of Health & Hum. Servs., 88 Fed. Cl. 706, 743 (2009) (quoting Gen. 28 Elec. Co. v. Joiner, 522 U.S. 136, 146 (1997)); see also D’Tiole v. Sec’y of Health & Hum. Servs., No. 15-085V, 2016 WL 7664475, at *24 (Fed. Cl. Spec. Mstr. Nov. 28, 2016) (stating that the Vaccine Act “require[s] a chain of reliable propositions supporting [a] petitioner’s theory”).

Under the second prong of Althen, a petitioner must prove that the vaccine actually did cause the alleged injury in a particular case. See Pafford, 2004 WL 1717359, at *4; Althen, 418 F.3d at 1279. The second Althen prong requires proof of a logical sequence of cause and effect, usually supported by facts derived from a petitioner’s medical records. Althen, 418 F.3d at 1278; Capizzano, 440 F.3d at 1326; Grant v. Sec’y of Health & Hum. Servs., 956 F.2d 1144, 1148 (Fed. Cir. 1992). A petitioner does not meet this obligation by showing only a temporal association between the vaccination and the injury; instead, the petitioner “must explain how and why the injury occurred.” Pafford, 2004 WL 1717359, at *4 (emphasis in original). The special master in Pafford noted petitioners “must prove [] both that her vaccinations were a substantial factor in causing the illness . . . and that the harm would not have occurred in the absence of the vaccination.” 2004 WL 1717359, at *4 (citing Shyface, 165 F.3d at 1352). A reputable medical or scientific explanation must support this logical sequence of cause and effect. Hodges v. Sec’y of Health & Hum. Servs., 9 F.3d 958, 961 (Fed. Cir. 1993) (citation omitted). Nevertheless, “[r]equiring epidemiologic studies . . . or general acceptance in the scientific or medical communities . . . impermissibly raises a claimant’s burden under the Vaccine Act and hinders the system created by Congress.” Capizzano, 440 F.3d at 1325–26. “[C]lose calls regarding causation are resolved in favor of injured claimants.” Althen 418 F.3d at 1280.

In Program cases, contemporaneous medical records and the opinions of treating physicians are favored. Capizzano, 440 F.3d at 1326 (citing Althen, 418 F.3d at 1280). Indeed, when reviewing the record, a special master must consider the opinions of treating physicians. Capizzano, 440 F.3d at 1326. This is because “treating physicians are likely to be in the best position to determine whether ‘a logical sequence of cause and effect show[s] that the vaccination was the reason for the injury.’” Id. In addition, “[m]edical records, in general, warrant consideration as trustworthy evidence. The records contain information supplied to or by health professionals to facilitate diagnosis and treatment of medical conditions. With proper treatment hanging in the balance, accuracy has an extra premium. These records are also generally contemporaneous to the medical events.” Cucuras v. Sec’y of Health & Hum. Servs., 993 F.2d 1525, 1528 (Fed. Cir. 1993). However, there is no “presumption that medical records are accurate and complete as to all of the patient’s physical conditions.” Kirby v. Sec’y of Health & Hum. Servs., 997 F.3d 1378, 1383 (Fed. Cir. 2021) (finding that a special master must consider the context of a medical encounter before concluding that it constitutes evidence regarding the absence of a condition). While a special master must consider these opinions and records, they are not “binding on the special master or court.” § 13(b)(1). Rather, when “evaluating the weight to be afforded to any such . . . [evidence], the special master . . . shall consider the entire record.” Id.

To satisfy the third Althen prong, a petitioner must establish a “proximate temporal relationship” between the vaccination and the alleged injury. Althen, 418 F.3d at 1281. This “requires preponderant proof that the onset of symptoms occurred within a timeframe for which, given the medical understanding of the disorder’s etiology, it is medically acceptable to finger causation-in-fact.” de Bazan v. Sec’y of Health & Hum. Servs., 539 F.3d 1347, 1352 (Fed. Cir. 2008). Typically, “a petitioner’s failure to satisfy the proximate temporal relationship prong is due to the fact that onset was too late after the administration of a vaccine for the vaccine to be the cause.” Id. However, “cases in which onset is too soon” also fail this prong; “in either case, the temporal relationship is not such that it is medically acceptable to conclude that the vaccination 29 and the injury are causally linked.” Id.; see also Locane v. Sec’y of Health & Hum. Servs., 685 F.3d 1375, 1381 (Fed. Cir. 2012) (“[If] the illness was present before the vaccine was administered, logically, the vaccine could not have caused the illness.”).

Although a temporal association alone is insufficient to establish causation, under the third prong of Althen, a petitioner must show that the timing of the injury fits with the causal theory. See Althen, 418 F.3d at 1278. The special master cannot infer causation from temporal proximity alone. See Thibaudeau v. Sec’y of Health & Hum. Servs., 24 Cl. Ct. 400, 403–04 (1991); see also Grant, 956 F.2d at 1148 (“[T]he inoculation is not the cause of every event that occurs within the ten[-]day period . . . [w]ithout more, this proximate temporal relationship will not support a finding of causation.” (quoting Hasler v. United States, 718 F.2d 202, 205 (6th Cir. 1983))).

A petitioner who satisfies all three prongs of the Althen test has established a prima facie showing of causation. Hammitt v. Sec’y of Health & Hum. Servs., 98 Fed. Cl. 719, 726 (2011). A petitioner who demonstrates by a preponderance of the evidence that he suffered an injury caused by vaccination is entitled to compensation unless the respondent can demonstrate by a preponderance of the evidence that the injury was caused by factors unrelated to the vaccination. See Althen, 418 F.3d at 1278; Knudsen, 35 F.3d at 547. In such a case, the government must not merely prove the existence of an alternative cause, but that such an alternative actually caused the injury. Kundsen, 35 F.3d at 549. Consequently, when and if the petitioner establishes a prima facie case, the burden the shifts to the government to prove that an alternative cause, unrelated to the administration of the vaccine, was the “sole substantial factor” in causing the alleged injury. See de Bazan, 539 F.3d at 1354; see also Hammitt, 98 Fed. Cl. at 726 (explaining that respondent’s burden is to show that the “factor unrelated” was the “sole substantial factor” in causing the injury). Additionally, a factor unrelated “may not include ‘any idiopathic, unexplained, unknown, hypothetical, or undocumentable cause, factor, injury, illness or condition.’” § 13(a)(2); see also Doe v. Sec’y of Health & Hum. Servs., 601 F.3d 1349 (Fed. Cir. 2010) (stating that an idiopathic diagnosis cannot be a “factor unrelated,” as it is idiopathic).

VI. Analysis

A. Prior Claims

In the past few years, there have been several Program cases that have alleged a GBS injury following Prevnar 13 vaccination with split results from the special masters. In cases where there is disagreement among special masters regarding asserted causation theories, the presiding special masters will often distinguish the most recent decision from previous decisions. These varying perspectives are not necessarily problematic as “Congress desired the special masters to have very wide discretion with respect to the evidence they would consider and the weight to be assigned that evidence.” Whitecotton v. Sec’y of Health & Hum. Servs., 81 F.3d 1099, 1108 (Fed. Cir. 1996). Furthermore, this is done notwithstanding the Circuit’s reaffirmance in Gamboa-Avila that “it was not arbitrary and capricious for a special master to make no attempt to distinguish the instant case from the other cases reaching opposite conclusions.” Gamboa-Avila v. Sec’y of Health & Hum. Servs., 166 F.4th 1318, 1323 (Fed. Cir. 2026) (citing Boatmon, 941 F.3d at 1358). It is also worth noting, as I have done here, that many cases alleging the same vaccine/injury cause-and-effect were done with experts that may overlap but are not the same on both sides; sharing theories that are similar but not identical; and using literature that has been at times, novel, outdated, updated, or even abandoned.

30 Several special masters have found in favor of petitioners relying on Dr. Steinman’s phosphoglycerol theory or some variation thereof.

1. Koller v. Sec’y of Health & Hum. Servs

In Koller, Dr. Steinman opined that the petitioner’s Miller Fisher variant of GBS was caused by Prevnar 13. Koller v. Sec’y of Health & Hum. Servs., No. 16-439V, 2021 WL 5027947, at *8 (Fed. Cl. Spec. Mstr. Oct. 8, 2021). Specifically, Dr. Steinman asserted that “it’s molecular mimicry to the phosphoglycerol that is connected to the polysaccharide structure of the vaccine that gives rise to GBS.” Id. Dr. Steinman continued that “[p]hosphoglycerol is the scaffold for the fatty acids that adorn the anus of the three carbon molecules of phosphoglycerol. Phosphoglycerol is thus a building block of the vaccine and also of the phospholipid” in myelin.” Id. at *9. The special master found unpersuasive the argument presented by Respondent’s expert, Dr. Leist, that “there is “no reliable medical literature supporting,” petitioner’s theory.” Id. at *19. He noted that identification and proof of specific biological mechanisms is not needed and found Dr. Steinman’s theory to be based on a sound and reliable scientific explanation. Id. at *20.

2. Parker v. Sec’y of Health & Hum. Servs.

In Parker, the petitioner’s expert, Dr. Gershwin, relied on Dr. Steinman’s molecular mimicry theory articulated in Koller, “as a springboard to review the literature cited and arrive at his own conclusions.” Parker v. Sec’y of Health & Hum. Servs., No. 20-411V, 2023 WL 9261248, at *10 (Fed. Cl. Spec. Mstr. Dec. 20, 2023). Dr. Gershwin opined that “the mimic is the phosphoglycerol structure within at least two serotypes of Prevnar, 18C and 23F. The cross- reactive mimic is phospholipid found within the myelin sheath of peripheral nerves, causing GBS.” Id. at *12. Respondent’s expert, Dr. He, argued that the lack of epidemiologic and mechanistic evidence was fatal to Dr. Gershwin’s theory. Id. In finding entitlement, the special master noted that Dr. He did “not refute the scientific data or foundational evidence used by Dr. Gershwin to support his theory.” Id. at *22. She noted that Dr. Gershwin relied on MS studies to show that “myelin phospholipids are targeted by an immune response, . . . that myelin is comprised of phospholipids, [] that phospholipids can serve as autoantigens in autoimmune disorders[, and] that patients with GBS have autoantibodies to phospholipids.” Id. Taken together, this “is sound support from reputable medical studies for the foundational aspects of Dr. Gershwin’s phosphoglycerol theory.” Id.

3. Davison v. Sec’y of Health & Hum. Servs.

In the Davison case, the petitioner relied on Dr. Steinman who proposed two molecular mimicry theories based on a phosphoglycerol theory and a CRM197 mimic, similar to the current case. Davison v. Sec’y of Health & Hum. Servs., No. 19-1404V, 2025 WL 2692664, at *7 (Fed. Cl. Spec. Mstr. Aug. 19, 2025). Again, the special master found in the petitioner’s favor, noting that scientific certainty is not the evidentiary standard and “[w]ith regard to the application of molecular mimicry, prior cases have expressed that the line must be drawn somewhere between speculation and certainty.” Id. at *12 (citing Brayboy v. Sec’y of Health & Human Servs., No. 15- 183V, 2021 WL 4453146, at *19 (Fed. Cl. Spec. Mstr. Aug. 30, 2021)). The special master further noted that Respondent’s immunology expert, Dr. Zhang, did “not specifically discuss any of Dr. Steinman’s more specific observations regarding the potential pathogenicity of phospholipid antibodies in GBS or any of the literature he relied upon.” Id. at *10. The special master found that Dr. Steinman presented supporting evidence for his assertions: 31 (1) the Prevnar 13 vaccine contains phosphoglycerol groups that are necessary to the vaccine’s immunogenicity[;] . . . (2) the phosphate portion of the phospholipid molecule has immune reactivity in myelin tissue, albeit demonstrated in the context of a different demyelinating condition ([MS])[;] . . . (3) GBS patients develop antiphospholipid antibodies[;] . . . and (4) these antibodies are cross-reactive with phospholipids present in myelin tissue.

Id. at *12. In response, Dr. Zhang’s rebuttal was focused on “fact that the wild S. pneumoniae infection has not been shown to cause GBS,” and the lack of epidemiological studies. Id. at *15. In his decision, the special master noted that “evidence of parallels to nature infection [] is never sufficient to either accept or reject a causal relationship.” Id. at *14 (citing Gaskin v. Sec’y of Health & Human Servs., No. 21-835V, 2025 WL 786306 at *12 (Fed. Cl. Spec. Mstr. Feb. 11, 2025)). He further noted that epidemiology is not necessary for a petitioner to be successful. Id. (citing Capizzano, 440 F.3d at 1325).

4. Fee v. Sec’y of Health & Hum. Servs.

In the Fee case, the petitioner’s expert, Dr. DeAngelo, also presented the theory “that molecular mimicry caused ‘a homologous interplay between the phosphoglycerol/phosphorylcholine within the Prevnar 13 vaccine and the phospholipid components in the human myelin sheath.’” Fee v. Sec’y of Health & Hum. Servs., No. 19-1979V, 2026 WL 700326, at *13 (Fed. Cl. Spec. Mstr. Feb. 13, 2026). As in Parker, Dr. He’s rebuttal warned against the overreliance on molecular mimicry in Program cases. Id. at *9. He criticized Dr. DeAngelo’s use of MS studies and the lack of supporting statistics. Id. Dr. He argued that it was “unclear whether GBS patients have similar types of autoantibodies targeting a phosphate group,” and there was “no evidence that these autoantibodies are the initiators of MS, let alone GBS.” Id. at *14. Dr. He also referred to the Institute of Medicine (“IOM”) stating “naturally occurring and postinfectious cross-reactive antibodies and T cells are relatively common and most frequently not pathogenic, and can also be secondary to a nonspecific tissue injury.” Id. In finding for petitioner, I noted that Dr. He “denounced molecular mimicry as a theory outright, contending that if it were true, all vaccines could cross-react to induce all kinds of autoimmune conditions.” Id. at *21. Dr. He did not refute the substance of Dr. DeAngelo’s theory, but instead argued that without epidemiologic evidence, a traditional criterion sanctioned by the IOM to prove molecular mimicry, the theory was insufficient. Id. I also noted that given the rare nature of many of the conditions seen in the Program and lack of testing practicality, epidemiological studies are not required. Id.

Other special masters have found this theory less persuasive.

5. Bielak v. Sec’y of Health & Hum. Servs.

In Bielak, the chief special master noted that molecular mimicry has been accepted as a biological mechanism for flu-vaccine caused GBS, and that there are “several evidentiary components” of causal association. Bielak v. Sec’y of Health & Hum. Servs., No. 18-761V, 2023 WL 35509, at *30 (Fed. Cl. Spec. Mstr. Jan. 3, 2023). First, “reliable science” has identified a specific autoantibody generated in response to C. jejuni that can cross-react with myelin gangliosides and cause autoimmune damage that manifests as motor axonal variant of GBS. Id. This supports molecular mimicry as a potential mechanism for other forms of GBS, “[a]nd there 32 is reliable evidence that the amino acid peptide sequences that make up different proteins could mimic aspects of myelin basic protein.” Id. Lastly, there is epidemiological evidence of increased GBS rates following a previously administered flu vaccine. Id. While this theory has since been asserted by petitioners as a causal mechanism for other vaccines, Bielak noted that the flu vaccine from the epidemiological study is an outlier, especially when compared to Prevnar 13. Id. at *31.

The chief special master noted the focus on “phospholipids common to the bacterial capsid antigens and the lipid content of myelin, attempting further to show the potential for cross-reactive harm by identifying antiphospholipid antibodies in the blood serum of GBS patients.” Bielak, 2023 WL 35509, at *33. Furthermore, Respondent’s expert, “Dr. Fujinami[,] did not dispute that some homologic commonalities were demonstrated through this aspect of [p]etitioner’s case.” Id. However, the chief special master ultimately found there was a lack of preponderant evidence 1) that Prevnar 13 produces pathogenic antibodies, and 2) that the relevant antibodies detected in GBS patients are caused by the disease as opposed to created by it. Id.

6. Gamboa-Avila v. Sec’y of Health & Hum. Servs.

The Federal Circuit weighed in on a later Prevnar 13/GBS opinion wherein the chief special master denied entitlement. Gamboa-Avila, 166 F.4th 1318. While the decision was based in part on “the absence of support in the medical literature for Dr. Steinman’s theories,” the Circuit reiterated that “[a] special master may weigh the fact that a ‘proposed mechanism had never been tested in any peer-reviewed study’ and may properly consider the weakness of medical literature support when evaluating the overall reliability of scientific evidence.” Id. at 6 (quoting Moberly, 592 F.3d at 1324); see Broekelschen v. Sec’y of Health & Hum. Servs., 618 F.3d 1339, 1350– 51(Fed. Cir. 2010). The chief special master identified very specific deficiencies in the asserted theory that caused for speculation below a more likely than not threshold. Id. at 7. The Circuit found that the chief “special master did not apply a standard inconsistent with [their decision in] Althen,” and his decision was not arbitrary and capricious. Id. There was some concern in the affirmance, however, regarding the “the inconsistent factual findings among the special masters on central issues presented in this case.” Id. The petitioner argued on appeal that the “findings in this case are inconsistent with those reached by other special masters on identical evidence in other cases.” Id. The Circuit also noted that the inconsistency in assessments by different special masters was noted in the entitlement denial. Id. at 8. The identity of the special master ultimately determined the outcome in this case. Id. Special masters were encouraged to recommend a Claims Court “related rule or other mechanisms to avoid inconsistent rulings.” Id.

7. Romine v. Sec’y of Health & Hum. Servs.

Since the Circuit’s finding in Gamboa-Avila, the Romine decision was published and included additional analysis to address some of the concerns articulated on appeal. Romine v. Sec’y of Health & Hum. Servs., No. 19-468V, 2026 WL 937898, at *7 (Fed. Cl. Spec. Mstr. Mar. 13, 2026). The special master began with analysis of the epidemiological evidence exploring possible relationships between pneumococcal vaccines and GBS and between the bacteria pneumococcus and GBS. Id. at *7–11. The special master found that “four large-scale epidemiological studies have looked for an increased risk of GBS after vaccines against S[.] pneumoniae[ and] did not find an increased risk.” Id. at *11. Additionally, the evidence submitted contained “no reports of a wild S[.] pneumoniae infection preceding GBS.” Id.

33 Dr. Steinman was also the petitioner’s expert in Romine, and he proposed a homology that he identified through BLAST searches. Romine, 2026 WL 937898, at *13–17. The special master held that the reliability standard for potentially relevant homologies was too generous based on the evidence. Id. at *16. Therefore, “any ensuing steps that follow from the BLAST searches are also problematic.” Id. Dr. Steinman reasoned that the body’s reaction to diphtheria toxin, a pathogen, would be similar to the protein CRM197 found in the Prevnar 13 because they share similar amino acid sequences. Id. Again, the special master found that Dr. Steinman’s reliance on homology was misplaced. Id. at *18. While CRM197, diphtheria toxin, and diphtheria toxoid have very similar amino-acid sequences, the biophysical, immunological, structural, and chemical differences mean that analyses of immune responses to diphtheria toxin/toxoid may not necessarily apply to CRM197. Id. Because of the numerous other concerns with the fundamental methodology behind Dr. Steinman’s reasoning, the decision did not reach the final step necessary for molecular mimicry. Id. at *15. The question of whether cross reactivity between identified components in Prevnar 13 and in human peripheral myelin “can contribute to the pathogenesis of GBS is not required, [and] can be reserved for another day.” Id.

In Romine, as in the present case, Dr. Steinman presented a variation on molecular mimicry in which “antibodies produced in response to a phosphate in the context of a polysaccharide[, a component of Prevnar 13] can cross-react with a phosphate in the context of a phospholipid[, a component of the myelin sheath].” Romine, 2026 WL 937898, at *29. The special master again found there was a lack of evidence generally to support GBS pathogenesis and specifically to support cross-reactivity. Id.

In an attempt to address the concerns expressed by the Circuit in Gamboa-Avila, the Romine decision included a discussion of how special masters may have come to different conclusions when presented with similar evidence in cases involving the same or similar vaccine and injury combinations. Romine, 2026 WL 937898, at * 29–33. Over 25 years ago, the Terran decision endorsed use of the Daubert factors “as a tool or framework for conducting the inquiry into the reliability of the evidence.” Terran, 195 F.3d at 1316. The Federal Circuit has continued to make clear that although peer reviewed studies are not required, “[a] special master may weigh the fact that a proposed mechanism had never been tested in any peer-reviewed study and may properly consider the weakness of medical literature support when evaluating the overall reliability of scientific evidence.” Gamboa-Avila, 166 F.4th at 1323 (citing Moberly, 592 F.3d at 1324). Indeed, in Romine, all four Daubert factors are articulated (testability, peer review, error rate, and general acceptance); however, the unique nature of the Program creates difficulties for the application of each one. Romine, 2026 WL 937898, at *33. While reiterating that “[t]he Daubert criteria should be employed flexibly,” the special master found it “difficult to see how [Dr. Steinman’s theories] pass[] any of the Daubert factors.” Id.

Various iterations of the two theories that Dr. Steinman has proposed in the present case have been previously asserted successfully and unsuccessfully in the Program, as discussed above. It is important to note that theory modifications based on a better understanding of how the immune system works (e.g., newly published research), observations of documented temporal associations between a specific vaccination and a specific injury (case studies), and consideration of specific case facts (positive antibody testing results) may have contributed to different conclusions in these cases. While I have considered the past findings of my colleagues and the evidence that they considered as detailed in their respective decisions, this Petitioner’s claim will be adjudicated based on the evidence contained within this case record.

34 We are cautious to not apply a one-size-fits-all approach in every case, because the nuance matters. Indeed, as the Program has evolved, renowned experts have presented novel theories that have been accepted or rejected based on the arguments and supporting literature presented to the special masters. For example, where there may have been no epidemiology for a specific theory, relevant studies have since been completed. See D’Tiole, 2016 WL 7664475 (the special master denying entitlement, in part, based on a 2014 epidemiological study that found no cases of the alleged injury, narcolepsy, following the relevant vaccine, FluMist). In another instance, ideas that were presented as plausible were not sufficiently developed to be reliable. See D’Angiolini v. Sec’y of Health & Hum. Servs., 122 Fed. Cl. 86, 101 (2015) (the Claims Court affirming the special master’s rejection of the ASIA theory by “the world’s preeminent expert in autoimmunity,” holding that the research is “still developing and currently incomplete”); see also Cerrone, 146 F.4th at 1121. There are however, many cases where the science is not proven, and yet we do not require specific causation evidence, because Table criteria have been accepted by medical experts retained by the United States government. Indeed, the Table, while efficient and consistent, is not ideal to settle complex and evolving disagreements between esteemed medical experts in their respective fields, that develop in real time. And so, a case-by-case analysis is needed. In such off- Table cases, Petitioner’s theory “must be supported by a sound and reliable medical or scientific explanation.” Andreu v. Sec’y of Health & Hum. Servs., 569 F.3d 1367, 1378 (Fed. Cir. 2009); Knudsen, 35 F.3d at 548. Presently, the alleged vaccine-cause injury is not a Table claim, but Petitioner draws many parallels between the Table flu/GBS injury and his off-Table claim to establish many of the parameters foundational to his asserted causation theory.

B. Althen Prong One

All the medical professionals in this case, including Petitioner’s treaters and the experts retained by Petitioner and Respondent, agree that the relevant condition is GBS. 53 Furthermore, there is no dispute of the underlying facts regarding the timing, onset, and nature of Petitioner’s symptoms. Indeed, the determinative issue in this case whether there is preponderant evidence of a causal mechanism for GBS following Prevnar 13 vaccination.

Under Althen prong one, Petitioner must set forth a medical theory explaining how the received vaccine could have caused or sustained injury. Andreu, 569 F.3d at 1375; Pafford, 451 F.3d at 1355–56. Petitioner’s theory of causation need not be medically or scientifically certain, but it must be informed by a “sound and reliable” medical or scientific explanation. Boatmon, 941 F.3d at 1359; see also Knudsen, 35 F.3c at 548; Veryzer v. Sec’y of Health & Hum. Servs., 98 Fed. Cl. 214, 223 (2011) (noting that special masters are bound by both § 13(b)(1) and Vaccine Rule 8(b)(1) to consider only evidence that is both “relevant” and “reliable”), aff’d 475 F. App’x 765 (Fed. Cir. 2012). If Petitioner relies upon a medical opinion to support his theory, the basis for the opinion and the reliability of that basis must be considered in the determination of how much weight to afford the offered opinion. See Broekelschen, 618 F.3d at 1347 (“The special master’s decision oftentimes is based on the credibility of the experts and the relative persuasiveness of their competing theories.”); Perriera v. Sec’y of Health & Hum. Servs., 33 F.3d 1375, 1377 n.6 (Fed. Cir. 1994) (stating that an “expert opinion is no better than the soundness of the reasons supporting it” (citing Fehrs v. United States, 620 F.2d 255 (Ct. Cl. 1980))). Importantly, as the Federal Circuit has made clear, “simply identifying a ‘plausible’ theory of causation is insufficient

53 Dr. Whitton noted that he is not a licensed doctor that diagnoses patients. He stated that “whenever I am invited to review a case, prior to accepting I invariably ensure that a board-certified MD will be retained to discuss the diagnosis and other clinical aspects of the case.” Resp’t’s Ex. C at 3. 35 for a petitioner to meet her burden of proof.” LaLonde, 746 F.3d at 1339. Instead, Petitioner must show it was more likely than not that the vaccine caused the condition alleged. Id.

Dr. Steinman’s molecular mimicry theory can be broken down into two main branches that he argues work together in this case, though both are capable of causing GBS independently. The first iteration asserts that two of the Prevnar 13 viral serotypes (18C and 23F) contain a phosphoglycerol moiety that is also central to the composition of phospholipids in the myelin that is damaged in GBS. These homologous sequences are molecular mimics wherein antibodies/autoantibodies can bind to either the antigen or the host tissue via the phosphate group. Dr. Steinman argued that studies on GBS patients have revealed the presence of these antibodies, thereby establishing a causal relationship with the disease. A birds-eye review of this theory appears reasonable and easy to follow. However, a more discerning review of the details begs the question: What evidence is there that antibodies produced to recognize specific pneumococcal vaccine serotypes will mistakenly target myelin tissue?

1. Phosphate Moiety Molecular Mimicry

a. MS v. GBS

The studies that Dr. Steinman relied on are largely in the context of MS. Indeed, the research on MS that Dr. Steinman and others have done has been nothing short of groundbreaking. While not conceding that Dr. Steinman’s MS research supports molecular mimicry as a pathogenic mechanism in humans, even Dr. Whitton acknowledged that “molecular mimicry can be found in people with MS.” Resp’t’s Ex. F at 19. He argued that the only article that definitively identifies molecular mimics, Lanz et al., found high affinity between EBNA1, a viral protein, and GlialCAM, a glycoprotein found in the CNS. Pet’r’s Ex. 67 at 1. This evidence clearly demonstrates molecular mimicry; however, the cross-reactivity between these two proteins is substantively different than the reaction that Dr. Steinman proposed in this case.

Comparing decisions that accept and reject Dr. Steinman’s theory, a critical factor that emerges is to what degree the evidence is found to support similarity between MS and GBS. In Davison, the special master found that “[w]hile the Ho [et al.] study pertained to [MS], there is no debate [] that [an] autoimmune attack on the myelin sheath is relevant to the pathogenesis of GBS[, and Nakos et al.] demonstrated the presence of phospholipid antibodies within GBS patients, but not controls.” Davison, 2025 WL 2692664, at *7. While antiganglioside antibodies are more commonly associated with GBS, “[w]e do not actually know the full scope of the antibodies that may be implicated in the pathology of GBS;” therefore, “the possibility of a glycolipid antigen remains.” Id. at *13 (internal citations omitted). There are two assumptions that must be made to complete this sequence. Pathogenic antibodies must be, at least in part, targeting the phospholipids and not just gangliosides, and the phospholipid antibodies here must be the cause as opposed to a result of demyelination. Dr. Whitton argued that the latter argument is directly undercut by the Gilburd et al. conclusion that the antibodies are “probably [] a result of the myelin damage or as a result of cross reaction with other anti-myelin antibodies.” Pet’r’s Ex. 55 at 6. This 30-year-old study does not consider some of the breakthroughs that have led to more researchers, including Dr. Steinman, questioning the role of antibodies in actual pathogenesis. However, even the most current studies concede that this question has not been answered.

Conversely, in Romine, the special master was unable to accept Dr. Steinman’s extrapolation of Ho et al. 2026 WL 937898, at *30. The special master noted that MS patients are 36 not routinely tested for anti-phospholipid antibodies and “the Lanz [et al.] paper proposes a protein as the target of autoimmune attack in [MS] and does not mention phospholipids as a possible target.” Id. at *25. The Ho et al. article noted that “lipids constitute 70% of the myelin sheath,” but the authors only go so far as to say “autoantibodies against lipids may contribute to the demyelination that characterizes [MS].” Pet’r’s Ex. 50 at 16 (emphasis added). Similarly, the Nakos et al. article cautioned that “no conclusive etiological concept [for GBS] has yet been found.” Pet’r’s Ex. 55 at 1. The authors were also very careful to note that that anti-phospholipid antibodies were found in patients with GBS. Id. at 1 (emphasis added).

Dr. Whitton’s argument highlighting differences between MS and GBS undercuts the use of MS research for GBS patients. MS is a CNS disease, while GBS is a peripheral neuropathy; because the diseases differ in their duration, pathogenesis, and treatment, Dr. Whitton argued that MS “is not appropriate to use [] as a model for GBS.” Resp’t’s Ex. C at 21. While the EBV/MS causal mechanism provides a roadmap for pathogenic molecular mimicry, there is no one-size- fits-all theory. Dr. Steinman’s theory is based on cross-reactivity between components in the Prevnar 13 vaccine and GBS, a peripheral neuropathy.

Dr. Steinman strongly disagreed with Dr. Whitton’s reading of Nakos et al. He argued that the quote, “It is not well understood whether these anti-phospholipid antibodies play a role in the pathogenesis of the polyneuropathy or represent a part of a more extensive immunoreaction that takes place in [] GBS,” was taken out of context. Pet’r’s Ex. 55 at 6. To put the quote in context, I will provide the entire paragraph:

It is not well understood whether these anti-phospholipid antibodies play a role in the pathogenesis of the polyneuropathy or represent a part of a more extensive immunoreaction that takes place in [] GBS. However, immunopathology in autopsies suggests that antibody mediated injury is a predominant disorder in the demyelinating form of GBS. The immune attack is directed against components of Schwann cell membrane and is accompanied by the characteristic feature of vesicular demyelination. Therefore it is crucial to investigate how anti- phospholipid antibodies are related to specific antigens in Schwann cell membrane.

Id. at 6–7. The article then identified the “prospective benefit[s]” of their findings: 1) “use [of] anti-phospholipid antibodies as an early additional marker of diagnostic significance;” and 2) use for “prognostic significance for GBS, as it may reflect the response to treatment.” Id. at 7. Notably, the authors did not suggest their findings be used to identify an etiological source or construct a theory of pathology. If this conclusion is as clear as Dr. Steinman suggests, the question begs, why do the authors not share his level of certainty, or at least suggest that their findings support that conclusion?

b. Prevnar 13 Target

According to Dr. Steinman, the antibody binds to “the phosphogylcerol moiety of the sugar as well as the sugars” in the 23F and 18C components of Prevnar 13. Pet’r’s Ex. 85 at 5. This assertion is one of the strongest areas of disagreement between him and Dr. Whitton. Dr. Whitton asserted that the Bryson et al. article “indisputably proves that the antibody predominantly recognizes the 23F bacterial polysaccharide, not the phosphoglycerol.” Resp’t’s Ex. C at 19. Both experts appear to recognize the importance of the polysaccharide for antibody recognition; however, Dr. Steinman argued that indeed “data from the Bryson [et al.] article demonstrates 37 UNEQUIVOCALLY that the immune response to the serotype 23F component of Pneumovax 23 targets the phosphoglycerol in serotype 23F.” Pet’r’s Ex. 85 at 6 (emphasis in original). Bryson et al. found that “[t]he electron density for the phosphate group[ is] another major binding determinant of the 23F polymer.” Pet’r’s Ex. 59 at 6. This result supports Dr. Steinman’s assertion that the phosphate group is a necessary condition for antibody recognition and binding; however, the authors further explained that “crystal structures of the [monosaccharide components of these polysaccharide complexes] reveal the basis for the high specificity of these [antibodies for the monosaccharide,] the key antigenic component of the [pneumococcal capsular polysaccharides] of S. pneumoniae serotype 23F.” Id. This conclusion supports Dr. Whitton’s assertion that “the epitope recognized by such an antibody would not be phosphoglycerol alone; rather, it would be a larger structure comprising phosphoglycerol + bacterial polysaccharide.” Resp’t’s Ex. C at 18. Figure two of the Bryson et al. article illustrates the “nine points of contact” between the 23F epitope and the antibody, and is further support for a hapten + carrier recognition and binding.

Pet’r’s Ex. 42 at 24, Figure S1.

There is preponderant evidence supporting Dr. Steinman’s assertion: the antibody does recognize the phosphate group. There is also preponderant evidence that the polysaccharide is the predominant target. This is further supported by the need for multiple serotypes within the conjugate vaccine to generate antibodies to different strains of S. pneumoniae.

c. Myelin Target

Dr. Steinman relied again on his MS research to opine that the phospholipids in the myelin sheath are targeted by antibodies in neuroinflammation. The Kanter et al. study noted the lipid specific autoimmunity in MS patients and hypothesized that “[t]he lipid molecules are thereby oriented so that the polar regions, such as the sulfate group or glycan molecule, are accessible for antibody binding.” Pet’r’s Ex. 50 at 6. They also noted that the “data suggest that sulfatide-specific and other lipid-specific responses can contribute to the pathogenesis of autoimmune demyelinating disease.” Id. Dr. Whitton quoted Dr. Steinman’s own research in rebuttal to this argument. “Autoimmune responses directed against phospholipids and gangliosides contribute to the pathogenesis in systemic lupus erythematosus and [GBS], respectively.” Id. at 1. In all of the 38 literature that Dr. Steinman submitted, including those on which he is a co-author, there is no assertion that phospholipids are the targets in GBS patients. Dr. Steinman is a co-author on many of these MS papers and his confidence in his own theory is undercut by no mention of GBS transferability in any of these papers. Instead, Dr. Steinman responded “that for the phosphate head group, [a central component to the antibodies and the phospholipids] there is a strong attraction for binding to these phosphate moiety, independent of what is attached to it.” Pet’r’s Ex. 85 at 6. He is again focused on the phosphate moiety and the ability of the antibodies to recognize it whether attached to the bacterial polysaccharide or the phospholipid myelin sheath. The MS studies that reveal anti-phospholipid antibodies are instructive for further study, but as stated previously, the diseases are not the same and one cannot be wholesale substituted for the other. He does not present direct evidence that the antibodies recognize any part of the phospholipid in GBS patients.

There is an additional hurdle that must be overcome even if one assumes that the antibodies are targeting phospholipids. Dr. Steinman quoted the Nakos et al. findings of phospholipid antibodies in GBS patients to establish pathology. However, the authors were unwilling to opine on the nature of the relationship between the antibodies and the disease and suggested additional research “to investigate how anti-phospholipid antibodies are related to specific antigens in Schwann cell membrane.” Pet’r’s 55 at 7. Indeed, there is no consensus in the medical community concerning whether the antibodies cause or result from GBS. Dr. Steinman relied on the Ho et al. article’s statement that “studies in EAE indicate that antibodies to oxidized phosphatidylcholine are generated as part of the pathological process of autoimmune demyelination.” Pet’r’s Ex. 59 at 9. But this statement is less instructive than their finding that “autoantibody targeting of oxidized phosphatidylcholine derivatives could conceivably contribute to MS pathogenesis by reducing the levels or blocking the immunoregulatory activity of these protective lipids.” Id. At this point, there is not preponderant evidence of causation.

d. Cross-Reactive Components

The next step in the first branch of Dr. Steinman’s theory after identifying the relevant components is establishing cross-reactivity. The experts for both parties sought to define relevant terms related to homologous groups. Initially, Dr. Steinman asserted that “phosphoglycerol is directly targeted by the core of the two human antibodies targeting 23F.” Pet’r’s Ex. 42 at 21. Dr. Whitton addressed this at length in his first report, and I included that analysis in an earlier section to provide some background information and show the degree of care that was taken by both experts to explain their positions thoroughly. Further discussion of that point is not necessary, because Dr. Steinman ultimately clarified that the phosphate moiety is the common component. He explained that “[t]he fact that the antibody binds to the phosphoglycerol moiety of the sugar as well as to the sugars is the basis for why the antibody to 23F and to other sugars containing phosphoglycerol, would trigger a ‘cross-reactive’ response to that component.” Pet’r’s Ex. 85 at 5–6. Put another way, Dr. Steinman appears to be saying that in Prevnar 13, the antibodies bind to specific saccharides plus the phosphate group in specific bacterial serotypes; and in the host tissue, the antibodies bind to the phosphoglycerol component of myelin lipids, such as phosphatidylcholine.

For comparison, I have again included the 23F serotype illustration highlighting the phosphoglycerol structure below, taken directly from the Bryson et al. article. This is followed by the structure of phosphatidylcholine and the location of the polar head groups targeted by antibodies, taken from Ho et al. 39 23F

Pet’r’s Ex. 59, Figure 2; Pet’r’s Ex. 51, Figure B.

A comparison of these two molecules reveals that they are similar but not the same. Dr. Steinman addressed this by way of his fighter jet analogy. This analogy, however, is an oversimplification of both processes and presents more questions than it answers. Dr. Steinman is correct that the hook is essential to a jet landing and remaining on the deck of an aircraft carrier. However, “[t]he carrier landing process involves the interaction of ship motions, the optical landing system, the pilot/aircraft combination, air wake disturbances and the landing signal officer. Therefore, the actual carrier approach is very demanding.” 54 In fact, without perfect synchronization of all of these moving parts, the fighter jet would be unable to land. It is unclear how the other essential landing gear would translate to the other components of Prevnar 13 or the myelin sheath to ensure antibody binding. This process is more consistent with Dr. Whitton’s explanation using the nine points of contact. And the Barbar et al. paper best makes the point that “the affinity for the hapten was shown to be modulated by the identity of the carrier molecule.” Pet’r’s Ex. 88 at 1. There is not preponderant evidence that the respective Prevnar 13 and myelin sheath phosphate moieties are sufficiently immunogenic to attract the relevant antibodies independent of the polysaccharide/lipid, nor that the phosphate moieties are sufficiently similar to each other attract the same antibodies.

54 Luis Hernando & R Martinez-Val, Preliminary Suitability Analysis of Carrier Approach Guidance and Recovery of Land-Based Aircraft, 230 J. AEROSPACE ENGINEERING 906 (2016). 40 e. Known Cross-Reactivity

Molecular mimicry involving vaccination inevitably raises the question about the corresponding wild antigen’s association with the relevant condition. In the most cited examples, the flu and COVID vaccines, both viral infections were linked to an increased rate of GBS. Dr. Whitton noted that many infections have been associated with GBS, but not S. pneumoniae. He explained that this may be because the bacteria identified as infectious triggers of GBS are gram negative with “outer membrane[s] in the surface of which are embedded the molecule that are thought to be involved to be in GBS.” Pet’r’s 42 at 11. S. pneumoniae is a gram-positive bacteria with a thick cellular wall and no outer membrane. This point is significant because the phosphoglycerol-containing polysaccharides that are targeted by the antibodies and induce GBS are also present in the bacterial strains. Dr. Steinman had no explanation for the significance or lack thereof of an outer membrane. Stepping back from the minutia of molecular mimicry, the relationship between a vaccine and the infection that it was designed to protect against is something that any lay person can understand. Instead of directly addressing this point, Dr. Steinman argued that vaccines are different from their corresponding bacteria, with the former acting as an immune system stimulus and the latter designed to “subvert the human immune system.” Pet’r’s 85 at 5. A more targeted response by Dr. Steinman could have done away with a point that would not have been fatal on its own, but is persuasive supporting evidence that the pieces of this theory may not fit.

Dr. Steinman emphasized that “sugars in the formulation of Prevnar 13 are combined with a foreign protein CRM197, that has one amino acid different than diphtheria toxin, and the sugars and the CRM197 are formulated with alum, a well-known adjuvant, added to boost the immune response.” Pet’r’s Ex. 85 at 4. Dr. Steinman does not provide persuasive evidence to explain how the alum component contributes to the development of GBS. Indeed, the vaccines commonly associated with GBS, seasonal flu vaccines, 55 and the Janssen Covid vaccine, do not contain an aluminum adjuvant. He does, in the second branch of his molecular mimicry theory, explain cross- reactivity involving CRM197.

2. BLAST Theory

a. Methodology

BLAST search-based cross-reactivity has been asserted in the Program by Dr. Steinman over the years with varying degrees of success. The criticism, largely the same, is also asserted here by Dr. Whitton. Dr. Whitton conceded that the Lanz et al. paper “confirms that short peptides can – sometimes – be recognized in a cross-reactive manner (something we have known for decades).” Resp’t’s Ex. F at 19. While homology can be evidence of cross-reactivity, even with short peptide chains, there must be some evidence that said cross-reactivity was harmful to the host in order to establish vaccine-caused disease via molecular mimicry. Dr. Whitton’s discussion of linear versus discontinuous antibody epitopes illustrated how short homologous chains can be folded into a 3D structure to form functional proteins “recognized by biologically-relevant antibodies.” Resp’t’s Ex. F at 13. In short, it is not how big the chain is, but how much it sparkles.

55 Fluad is an inactivated, adjuvanted flu vaccine approved for people 65 years and older to help create a stronger immune response. Different Types of Flu Vaccines, Centers for Disease Control, https://www.cdc .gov/flu/vaccine-types (last visited May 1, 2026). 41 Dr. Whitton attacked Dr. Steinman’s methodology as overbroad and cherry picked. He explained that Dr. Steinman’s search parameters for his BLASTs were so inclusive, the results are all identified by the search engine as “chance findings.” Resp’t’s Ex. C at 49. Dr. Steinman does not dispute the commonality problem that presents itself when you conduct short searches. He countered this criticism with an explanation of his multi-step filtration process to identify and disregard false positives. Dr. Steinman’s starting point is not his end result. The fact that he begins with a broad set of parameters could ensure that he does not miss relevant sequences. This initial screening does not render his process unreliable. Aside from the argument that Dr. Steinman can always find homology because his parameters are too generous, Dr. Whitton also took issue with his methodology for immunological relevance. This step of the process is the deciding factor for identifying epitopes capable of pathological cross-reactivity. It is there that Dr. Steinman’s explanation of the process is less persuasive.

b. Mimic Identification

Dr. Steinman began with CRM197, and Dr. Whitton agreed with the immunogenic relevance of CRM197, despite the disagreement over the type of molecule and its purpose. Although Dr. Steinman focused on contactin-1 as the mimic, in a supplemental report he also discussed GlialCAM. “The paranodal proteins, contactin, contactin-associated protein and neurofascin are members of this family and share significant homology with GlialCAM.” Pet’r’s Ex. 85 at 21. Dr. Whitton pointed out that in his published papers, “Dr. Steinman and colleagues are telling the world that GlialCAM protein is the target of autoimmune assault, triggering MS; while in the Court, Dr. Steinman asserts that phosphoglycerol, phospholipids, and phosphate are the targets in MS (and therefore, he claims, in GBS).” Resp’t’s Ex. C at 62. These papers, Dr. Steinman further noted, reported that antibodies to paranodal proteins are found in GBS patients. Pet’r’s Ex. 85 at 21. The Lanz et al. article provided evidence that GlialCAM cross-reacts with EBNA1 to potentially cause MS. The Bjornevik et al. “findings strongly suggest that the occurrence of EBV infection, detectable by the elicited immune response, is a cause and not a consequence of MS.” Pet’r’s Ex. 69 at 3. This reference to MS carries the same assumptions inherent in the first iteration of his theory that the two diseases are inherently similar enough that the molecular mimicry process would rely on the same sequences. The application of this study is further complicated by the fact that the mimic is a peptide in a viral protein (EBNA 1) versus a bacterial serotype within a conjugated vaccine (S. pneumoniae). Dr. Steinman’s sequence of cause and effect begins with 1) a causal relationship between EBV and MS (established by Bjornevik et al.) that is the foundation for asserting that 2) the antibodies in MS patients that cross react to EBNA1 and GlialCAM (Lanz et al.) are evidence of a molecular mimicry pathogenesis. These antibodies would also, pursuant to Dr. Steinman’s theory, 3) bind to other paranodal proteins, including contactin because of their shared homology and 4) result in GBS. Repeatedly, Dr. Steinman appears to conflate cross-reactivity with pathology without evidence to support such a conclusion. He does not dispute Dr. Whitton’s assertion that benign cross-reactivity is common. He also does not dispute that antibodies are not always the harbingers of disease. While the evidentiary standard that petitioners must meet is deliberately and significantly lower than what is necessary within the medical field for certainty, Dr. Steinman’s theory demands several leaps of reason that may be possible but are currently based on speculative proclamations.

c. WEQAKALSVE

Using a Pubmed BLAST search algorithm, Dr. Steinman queried contactin-1 versus CRM197 and discovered “[t]he sequence WEQAKALSVE has five of ten identical amino acids, 42 and thus would be a region that [] might be capable of inducing a neuroinflammatory disease.” Pet’r’s Ex. 85 at 29. Dr. Steinman identified another sequence, WDHVVALSNE, but Dr. Whitton argued that he “fails to present any immunological information regarding the contactin-1 sequence WDHVVALSNE, which differs by [five] amino acids from the CRM197 sequence.” Resp’t’s Ex. C at 45. He argued that “Dr. Steinman appears to simply assume (and to ask the Court to assume) that any immune response that recognizes WEQAKALSVE must also recognize WDHVVALSNE.” Id. at 46. Without further explanations from Dr. Steinman, this is yet another gap that must be filled by speculation.

d. Immunogenicity

Dr. Steinman asserted that his BLAST search and filtration process not only identifies relevant homologous epitopes but also provides evidence of immunogenicity necessary for pathogenesis. In order to establish that homologous parts of the mimics he found in CRM197 and contactin-1 were relevant immunogenic epitopes, Dr. Steinman “filtered his results through the IEDB tool.” Pet’r’s Ex. 85 at 31. Dr. Steinman’s process revealed that the WEQAKALSVE sequence “is an epitope in diphtheria toxin, which has only one amino acid difference from CRM197.” Id. Dr. Whitton argued that the sequences selected by Dr. Steinman to compare were not actual sequences that had been shown to activate the human immune system. Instead, WDHVVALSNE was not categorized by the BLAST search tool as an immunogenic sequence at all. Eventually, the BLAST search tool revealed that WEQAKALSVE was contained within a 20- amino-acid-long sequence that did not, in total, share meaningful homology with contactin-1. Dr. Whitton arrived at a 20-amino-acid-long sequence (NNWEQAKALSVELEINFETR) which Raju et al. determined “could activate some human CD4+ T cells.” Resp’t’s Ex. C at 50 (citing Pet’r’s Ex. 74). However, Dr. Steinman did not explain why these specific homologous sections that he selected are the immunologically significant acids within the complete, immunologically significant epitope. His assertion that the WEQAKLALSVE is itself an epitope is disproven by Dr. Whitton’s illustrative BLAST search results. After entering the sequence into the entry box, with settings to search for linear epitopes, there were “No Results to display.” Resp’t’s Ex. C at 50.

3. Epidemiological Studies

Within the medical community, epidemiological studies are considered among the best types of evidence. In the Program, they have been used as a basis for Table claims, which when specific criteria are met, provide a presumption of causation for the Petitioner that can then be rebutted by Respondent. Due to the rare occurrence rate of many of the injuries that are examined in the Vaccine Program, it is often difficult, if not impossible, to find relevant, large-scale studies that prove or disprove vaccine causation. Consequently, “petitioners are not required to support their claims with epidemiology.” Romine, 2026 WL 937898, at *35 (citing Althen at 1279–81). However, to the extent that studies do exist, they can be used to support or rebut a theory that a petitioner presents. Lampe, 219 F.3d at 1365; McCollum v. Sec’y of Health & Hum. Servs., 760 Fed App’x 1003, 1008 (Fed. Cir. 2019). In Romine, the special master noted that this is one of those rare instances wherein there are multiple large-scale studies and suggested “if a pneumococcal vaccine were increasing the incidence of GBS, one of these studies would have detected an uptick.” Id. at *28. In the majority of cases, the lack of epidemiological studies supporting Petitioner’s theory is a point that Respondent will mention, even as he acknowledges that such studies are not required. This fact is rarely probative. However, “in a case like the present, where a vaccine’s formulation bears heavily on Petitioner’s causation claim, and where Petitioner 43 wants to leverage findings about a different vaccine formulation, epidemiologic evidence relevant to the version of the vaccine in dispute ought to be weighed against Petitioner’s proof in evaluating whether he has carried his overall burden.” D’Tiole, 2016 WL 7664475, at *22; see W.C. v. Sec’y of Health & Hum. Servs., 704 F.3d 1352, 1361 (Fed. Cir. 2013) (holding the special master was not arbitrary in denying compensation and noting that the special master properly relied on several epidemiological studies in reaching his decision). While the Haber et al. and Tseng et al. studies are not determinative, these two articles, as also noted in Romine, underscore why epidemiological studies can be persuasive.

Dr. Steinman argued that while GBS is a common neuropathy, it is “a relatively rare illness,” particularly following any vaccination. Pet’r’s Ex. 42 at 41. As a result, it is unlikely that a causal relationship would be statistically detectable, in an epidemiological study. Dr. Steinman also argued the relevant studies that have been done have been unable to definitively rule out a causal relationship between Prevnar 13 and GBS. In his first report, Dr. Steinman included a section entitled “Case Reports and Epidemiologic Studies,” and briefly discussed Haber et al. Id. In a later section on timing, Dr. Steinman acknowledged that “there is no [] detailed epidemiologic data specific to Prevnar 13 and GBS for the Petitioner to show.” Id. at 42. Instead, he relied on large scale studies of the swine flu vaccine/GBS and EBV/MS relationships. See id. at 26–28; Pet’r’s Ex. 85 at 40. Dr. Whitton asserted that there are no epidemiological studies to support any theory that Prevnar 13 can cause GBS; furthermore, he argued that Haber et al. and Tseng et al. both undercut Dr. Steinman’s theory. The Haber et al. study explicitly noted “no disproportionate reporting for GBS” following approximately 16 million Prevnar 13 vaccinations over a three-year- period. Pet’r’s Ex 83 at 4. While these numbers are compelling, it should be noted that this is a passive study comprised of VAERS data. This type of data is frequently attacked by Respondent as being low order due to the self-reporting nature of VAERS, and it would certainly be insufficient to establish any point without more. VAERS also includes anecdotal coincidences but can be compared to baseline population numbers for diseases that are often idiopathic. Given the low bar for submission, it is worth noting that this study’s results did not indicate a potential causal relationship and supplements the other medical literature that has been filed. Tseng et al. likewise found no significantly elevated risk of GBS following a review of over 300,000 Prevnar 13 vaccinations. Resp’t’s Ex. A, Tab 13 at 4. Without understanding the etiology of many diseases, epidemiologic studies may be the only way to determine causation. The absence of a study does not reveal the lack of a connection; however, a completed study can reinforce inconsistencies in causation theories that may lead to modification or rejection of the mechanism. The results from Haber et al. belie Dr. Steinman’s claim that the rarity of the vaccination and the disease would prevent the discovery of any increased risk. Likewise, the Tseng et al. study analyzed the development of GBS following two different pneumococcal vaccines with no increased risk for either in support of Dr. Whitton’s assertion that there is no connection between the underlying virus that would also apply to the vaccine.

4. Preponderant Evidence

Dr. Steinman presented a theory that included parallel processes of Prevnar 13 induced GBS. He provided a roadmap for molecular mimicry. He also provided support for his assertion that short peptide chains can, in rare instances, be sufficient for cross-reactivity. Indeed, it was only after consideration of all of the evidence presented by him and Dr. Whitton that the parts seemed not to equal the whole. Dr. Steinman did not persuasively explain why studies that focused on MS should be so directly applied to GBS. We have an example of an infectious agent causally related to GBS, but live C. jejuni induces the production of autoantibodies that attack neuronal 44 gangliosides, unlike the phospholipids targeted pursuant to Dr. Steinman’s theory with respect to Prevnar 13. The MS studies highlight the role of antiphospholipid antibodies and their potential causal relationship, but the Prevnar 13 vaccine serotypes are composed of polysaccharides with phosphate moieties. Dr. Steinman’s bridge from sugar to fat consists of iterations of a phosphate group that, at best, are only recognizable when attached to an antibody in the context of a larger epitope. Dr. Steinman did not present preponderant evidence that phosphate moiety was the main antibody binding site, such that the attached lipid or saccharide, was inconsequential. Lastly, there is no preponderant evidence in the record that even if cross-reactivity did occur, that GBS would result.

Indeed, there are many conditions that can be categorized as neuropathies, and there are often acute and chronic conditions that share symptoms. For example, MS is a chronic condition that shares symptomology with transverse myelitis, so much so that MS is commonly misdiagnosed as transverse myelitis until the symptoms are no longer indicative of an acute condition. In a 2022 decision, I found, partly due to the similarities between the two neuropathies, that Dr. Steinman was able to apply his MS research to transverse myelitis following Prevnar 13 vaccination. Tracy v. Health and Human Servs., No. 16-213V, 2022 WL 1125281 (Fed. Cl. Spec. Mstr. Mar. 30, 2022). During his testimony at hearing in that case, Dr. Steinman presented his theory, “and I was seeking for [Respondent’s expert] to highlight flaws in that mechanism. Instead, he acknowledged that Petitioners’ theory is not impossible, . . . he just does not believe it applies in [Petitioners’] case pursuant to Althen prong two.” Id. at *40. I also noted that while Respondent’s expert “argued that [the filed] articles are inapplicable because the pathological process involved in molecular mimicry would be different in patients with MS compared to those with TM, he did not explain why or how.” Id.

GBS (AIDP) also has a chronic counterpart, CIDP. These two diseases are not the same, but they present similarly with the latter often misdiagnosed as the former at initial presentation. Following Dr. Steinman’s logic, would the same mechanism apply to CIDP, given its similarities to GBS? Dr. Steinman has not placed limits on his theory and both experts agree on the specific and rare nature of pathogenic molecular mimicry, especially in the context of vaccination. Althen does not require certainty, but it does require a theory to go beyond plausibility to more likely than not. See Cerrone, 146 F.4th at 1121; see also Moberly, 592 F.3d at 1322; LaLonde, 746 F.3d at 1339. It also requires a reliable showing of how the vaccine at issue can cause the type of injury alleged. After careful consideration of all of the evidence, Petitioner has not provided preponderant evidence of general causation pursuant to Althen prong one.

C. Althen Prong Two

Under Althen prong two, Petitioner must prove by a preponderance of the evidence that there is a “logical sequence of cause and effect showing that the vaccination was the reason for the injury.” Capizzano, 440 F.3d at 1324 (quoting Althen, 418 F.3d at 1278). “Petitioner must show that the vaccine was the ‘but for’ cause of the harm . . . or in other words, that the vaccine was the ‘reason for the injury.’” Pafford, 451 F.3d at 1356 (internal citations omitted). This includes instances where an action is “a substantial factor in bringing about the harm, and that the harm would not have occurred but for that action.” Shyface, 165 F.3d at 1365 (internal citations omitted). The Federal Circuit has explained that in such cases, “while the vaccination must be a substantial factor in the [injury], it need not be the sole factor or even the predominate factor.” Pafford, 451 F.3d at 1357.

45 In evaluating whether this prong is satisfied, the opinions and views of the vaccinee’s treating physicians are entitled to some weight. Andreu, 569 F.3d at 1367; Capizzano, 440 F.3d at 1326 (“[M]edical records and medical opinion testimony are favored in vaccine cases, as treating physicians are likely to be in the best position to determine whether a ‘logical sequence of cause- and-effect show[s] that the vaccination was the reason for the injury.’” (quoting Althen, 418 F.3d at 1280)). Medical records are generally viewed as trustworthy evidence, since they are created contemporaneously with the treatment of the vaccinee. Curcuras, 993 F.2d at 1528. Petitioner need not make a specific type of evidentiary showing, i.e., “epidemiologic studies, rechallenge, the presence of pathological markers or genetic predisposition, or general acceptance in the scientific or medical communities to establish a logical sequence of cause and effect.” Capizzano, 400 F.3d at 1325. Instead, Petitioner may satisfy his burden by presenting circumstantial evidence and reliable medical opinions. Id. at 1325–26.

Petitioner’s treaters referenced both his pneumococcal vaccine and URI in medical records during the diagnosis and treatment of his GBS. See Pet’r’s Ex. 3 at 12; Pet’r’s Ex. 38 at 65, 159. Petitioner’s medical history also lists Prevnar 13 under Allergens. Pet’r’s Ex. 3 at 14. Notwithstanding these notations, none of Petitioner’s treaters opine that he developed GBS due his vaccination. Indeed, the nurse practitioner who treated Petitioner during his June 2018 hospitalization characterized his facial palsy as a “possible extension of AIDP” and suggested a recent URI etiology. Pet’r’s Ex. 38 at 122. Ultimately, there is no evidence in the records that Petitioner’s treatment course was dictated by any specific etiology.

To meet his burden pursuant to Althen prong two, a petitioner must first meet his burden pursuant to prong one. The prong two evidentiary showing is informally referred to as specific causation, because the clinical presentation (specific factual history) cannot be assessed for a logical sequence of cause and effect without a sound and reliability (general) theory to provide context. In this case, Petitioner presented two iterations of a molecular mimicry theory, however the evidence did not meet the preponderant standard. Dr. Steinman did however, address the evidence related to Althen prong two in both of his reports with the same passage. “A logical sequence of cause and effect showing that the vaccination was the reason for the injury: The vaccine has constituents that induce antibodies known to cross-react with myelin proteins and lipids and that are found in patients with GBS.” Pet’r’s Exs. 42 at 42; Pet’r’s Ex. 85 at 42. The conclusion does not explain how Prevnar 13 was a substantial factor in the manifestation of Petitioner’s GBS. Dr. Steinman does not articulate how to identify a GBS case with a Prevnar 13 etiology.

As evidence of a logical sequence of cause and effect, Petitioner asserted that his GBS diagnosis was undisputed; the temporal relationship between his vaccination and disease progression was consistent with the “latency and nadir of [GBS] after exposure;” Prevnar 13 is a listed as an allergen associated with GBS, and there is no evidence of an alternative cause. Pet’r’s Mot. at 27–28. Respondent countered that “[d]emonstrating a logical sequence of cause and effect under Althen is not simply a matter of confirming that [P]etitioner received a Prevnar-13 vaccine and later suffered GBS.” Resp’t’s Response at 23. Indeed, this account by Petitioner is simply a restatement of the alleged cause and the effect. The logical sequence must consist of more than a temporal relationship and lack of alternative cause. Capizzano, 440 F.3d at 1326–27. Petitioner has failed to meet his burden pursuant to Althen prong two.

46 D. Althen Prong Three

Althen prong three requires Petitioner to establish a “proximate temporal relationship” between the vaccination and the injury alleged. Althen, 418 F.3d at 1281. Petitioner must offer “preponderant proof that the onset of symptoms occurred within a timeframe for which, given the medical understanding of the disorder’s etiology, is medically acceptable to infer causation-in- fact.” de Bazan, 539 F.3d at 1352. The explanation for what is a medically acceptable timeframe must also coincide with the theory of how the relevant vaccine can cause the injury alleged (under Althen prong one). Id.; Koehn v. Sec’y of Health & Hum. Servs., 773 F.3d at 1239, 1243 (Fed. Cir. 2014); Shapiro, 101 Fed. Cl. at 542; see Pafford, 451 F.3d at 1358. A temporal relationship between a vaccine and an injury, standing alone, does not constitute preponderant evidence of vaccine causation. See, e.g., Veryzer v. Sec’y of Health & Hum. Servs., 100 Fed. Cl. 344, 356 (2011) (explaining that “a temporal relationship alone will not demonstrate the requisite causal link and that [P]etitioner must posit a medical theory causally connecting the vaccine and injury”).

Petitioner received the Prevnar 13 vaccine on May 21, 2018, and sought medical treatment approximately two-and-a-half weeks later, on June 7, 2018, with complaints of numbness and tingling in all four extremities. Petitioner was seen again, within the following week with symptom progression and GBS was first considered. His CT was abnormal and his treaters noted a preceding URI and his Prevnar 13 vaccine. Dr. Steinman identified Petitioner’s onset of symptoms at 17 days as appropriate and relied on the timeline from epidemiologic data supporting a causal connection between the 1976 swine flu vaccine and GBS when onset occurred two to 34 days post inoculation. This extrapolation is consistent with Dr. Steinman’s reliance on other more established principles of vaccine injury causation to assert his causation theory with respect to GBS following Prevnar 13 vaccination, including molecular mimicry generally and specific cross-reactivity targets in peripheral neuropathy. Dr. Jameison argued that “Dr. Steinman did not explain how this historical paper evaluating the incidence GBS after vaccination against pandemic influenza in the winter of 1976 to 1977 supports molecular mimicry as a mechanism for the Prevenar 13 vaccination in 2018.” Resp’t’s Ex. A at 10. While Dr. Jameison agreed that Petitioner’s GBS “symptom onset was approximately two weeks after receiving a [Prevnar 13 vaccination],” she opined that there was no evidence submitted that defined an appropriate causal timeframe. Id. at 11. She noted that Dr. Steinman’s reference to a historical event involving the swine flu virus vaccine is not instructive for a bacterial vaccine. Id. Dr. Steinman responded to Dr. Jameison’s criticism by citing to examples of GBS cases that were studied in part because of their temporal relationship to Prevnar 13 vaccination. He noted that median time from vaccination to symptom onset was nine days. Pet’r’s Ex. 42 at 41. Temporal relationships alone cannot establish causality; however, the symptom onset time that is consistent with Petitioner’s asserted biological mechanism is persuasive in the context of a well-reasoned theory. In the present case, the temporal relationship is consistent with a Table flu/GBS, and it is consistent with the cases referenced by Dr. Steinman. However, that evidence does not preponderantly establish what an appropriate temporal relationship for GBS via molecular mimicry is following Prevnar 13 vaccination. It would be speculation to assume the molecular mimicry would have the same timeframe in every case of disease pathogenesis, particularly given the varying lead times of autoimmune neuropathies. Accordingly, I find the evidence does not establish by a preponderant of the evidence whether Petitioner’s onset timing is consistent with a proximate temporal relationship between the alleged vaccination and injury. See Althen, 418 F.3d at 1278. That determination can only be made when there is preponderant evidence of a causal theory for context.

47 I should note that I have previously found that the time frame identified for Table flu/GBS case is applicable to molecular mimicry theories generally. As I have stated previously in this decision, in order to properly compare the findings in cases that appear to present similar evidence, it is imperative to examine each submitted record. In Fee, for example, Respondent’s expert did “not contest whether Petitioner’s eight-day onset [was] appropriate, and Respondent pose[d] no objection to the proposed timing of Petitioner’s theory.” Fee, 2026 WL 700326, at *27. There, based on the unrebutted evidence, I found that Petitioner had presented preponderant evidence of appropriate timing. In the present case, different experts on behalf of Respondent did not concede any aspect of Petitioner’s theory and challenged all of Dr. Steinman’s assertions.

E. Alternative Causation

Because I do not conclude that Petitioner established a prima facie case, Respondent is under no obligation to submit any evidence of alternative causation. Whitecotton v. Sec’y of Health & Hum. Servs., 17 F.3d 374, 376 (Fed. Cir. 1994), rev’d on other grounds sub nom., Shalala v. Whitecotton, 514 U.S. 268 (1995); see also Walther v. Sec’y of Health & Hum. Servs., 485 F.3d 1146, 1151 (Fed. Cir. 2007). However, Respondent’s experts contend that it is much more likely that Petitioner’s GBS is the result of an unidentified URI that was referenced in Petitioner’s medical records due to the high correlation between GBS and infection generally. See Pet’r’s Ex. 38 at 65; 35 at 122. Dr. Whitton noted that “[a]pproximately [two-thirds] of GBS cases are preceded by signs and/or symptoms of an infection, often of the respiratory or GI tracts.” Resp’t’s Ex. C at 9. Also, Dr. Steinman explained that NINDS defines GBS as a rare syndrome that usually “occurs a few days or weeks after the patient has had symptoms of a respiratory or gastrointestinal viral infection.” Pet’r’s Ex. 42 at 14. From a purely statistical perspective, it is more likely that Petitioner developed an infection that led to his GBS. The references in Petitioner’s medical record to a URI are vague but provide some support for Respondent’s contention. I do not find that this evidence meets the preponderant standard to determine alternative causation here, however the evidence that Respondent identified is persuasive counterevidence to Petitioner’s theory. Ultimately because Petitioner did not meet his burden pursuant to Althen, it is not necessary to make a finding with respect to Respondent’s asserted alternative cause.

VII. Conclusion

The biological mechanism that Dr. Steinman has presented is his signature theory, supported by many co-authored articles, and it has shaped our understanding of molecular mimicry and the pathology of neurology in the medical community and this Program. As it has evolved over the course of many years, new studies have revealed more information about antibody- mediated disease and gotten us closer to understanding the how and why of many autoimmune diseases. Although more is known about these processes now than when Dr. Steinman first introduced this theory, gaps in the reasoning remain. That is not to say that, like the breakthrough 2022 paper establishing a viral etiology for MS, we are not on the cusp of such a development in understanding GBS. A sound and reliable theory requires all these pieces working together, even if it is not quite understood how. D’Tiole, 2016 WL 7664475, at *24 (stating that the Vaccine Act “require[s] a chain of reliable propositions supporting [a] petitioner’s theory”). This is where the presented theory fails. See Cedillo, 617 F.3d at 1339 (recognizing that a court may find that there is a gap between the data and the opinion). For the reasons discussed above, I find that Petitioner has not established by preponderant evidence that his Prevnar 13 vaccine caused his GBS.

48 After a careful review of the record, Petitioner has failed to provide preponderant evidence that his May 21, 2018 Prevnar 13 vaccine caused his GBS. Accordingly, Petitioner’s claim is DENIED. Absent a timely motion for review, the Clerk is directed to enter judgment dismissing this case for insufficient proof in accordance with Vaccine Rule 11(a). 56

IT IS SO ORDERED.

s/Herbrina D. S. Young Herbrina D. S. Young Special Master

56 Pursuant to Vaccine Rule 11(a), entry of judgment is expedited by the parties’ joint filing of a notice renouncing the right to seek review. 49