VICP Registry Case Source Bundle
Canonical URL: https://vicp-registry.org/case/USCOURTS-cofc-1_17-vv-00501
Package ID: USCOURTS-cofc-1_17-vv-00501
Petitioner: Berlin Bravo
Filed: 2017-04-10
Decided: 2023-05-31
Vaccine: HPV
Vaccination date: 2014-03-21
Condition: multiple sclerosis
Outcome: denied
Award amount USD: 

AI-assisted case summary:
Berlin Bravo, born in 1999, filed a claim alleging that her third dose of the human papillomavirus (HPV) vaccine, administered on March 21, 2014, either caused her to develop multiple sclerosis (MS) or significantly aggravated a pre-existing, undiagnosed case of MS. The Secretary of Health and Human Services disputed these claims. The case was adjudicated by Special Master Christian J. Moran. Petitioner was represented by Sol P. Ajalat of Ajalat & Ajalat, LLP, and Respondent was represented by Colleen Hartley of the United States Department of Justice. The Special Master issued a published decision denying entitlement on May 31, 2023.

Initially, Ms. Bravo alleged that the HPV vaccine was the cause-in-fact of her MS. However, the Special Master found that the evidence preponderated in favor of Ms. Bravo having suffered from undiagnosed multiple sclerosis before receiving the vaccine. This finding was based on imaging from a May 2, 2014 MRI, which revealed lesions, including a "black hole" lesion in the left frontal region, that experts agreed must have predated the vaccination. Dr. Subramaniam Sriram, a neurologist for the respondent, opined that this lesion indicated a chronic abnormality preceding the vaccination date. Dr. David Wilson, a neuroradiologist retained by the petitioner, also agreed that a juxtacortical lesion discussed in his report predated the vaccination, although he initially maintained it was not related to MS. Dr. Jonathan Kleefield, a neuroradiologist for the respondent, also concluded that the overwhelming majority of lesions were typical for demyelinating disease and indicated a chronic abnormality preceding the vaccination. Due to this finding, Ms. Bravo could not prevail on a causation-in-fact theory. The case then proceeded as a significant aggravation claim.

Ms. Bravo presented several theories for how the HPV vaccine could have significantly aggravated her MS, including molecular mimicry, the persistence of alum causing neurotoxicity, and alum leading to IL-1beta. She retained experts such as neurologist Lawrence Steinman, immunologist Yehuda Shoenfeld, pathologist Sin Hang Lee, and Ph.D. researcher Christopher Shaw. The Secretary retained neurologist Subramaniam Sriram, immunologist Neil Romberg, and neuroradiologist Jonathan Kleefield.

The Special Master found Ms. Bravo's theories unpersuasive. Regarding molecular mimicry, the Special Master noted inconsistencies with large epidemiological studies (Scheller and Mouchet) that did not associate the HPV vaccine with an increased risk of MS. The court also found that short amino acid sequence similarities are common and that Ms. Bravo and her experts failed to establish that any identified similarities were biologically relevant or that attacks on specific proteins like myelin basic protein or myelin oligodendrocyte-glycoprotein would worsen MS. The Special Master also found that Ms. Bravo failed to establish a logical sequence of cause and effect linking the vaccine to her specific condition, noting the absence of affirmative statements from treating physicians, such as Dr. Langer-Gould, who treated Ms. Bravo but did not connect her HPV vaccination to her MS in her records.

Regarding the theory of alum persistence and neurotoxicity, the Special Master cited a study (Linneberg) showing no increased risk of autoimmune diseases, including MS, in individuals receiving immunotherapy with aluminum hydroxide adjuvant. The Special Master also noted that the amount of aluminum in an HPV vaccine is significantly less than amounts used in experimental studies potentially showing harm.

For the theory of alum leading to IL-1beta, the Special Master noted that Ms. Bravo did not meaningfully advance this theory in her briefs and that caselaw trends against such theories. The Special Master also referenced prior decisions where similar theories involving alum and cytokines were rejected.

While Ms. Bravo presented evidence of a temporal association, with optic neuritis manifesting approximately five weeks after her final HPV vaccination, the Special Master stated that temporal association alone is insufficient to establish causation. The Special Master concluded that Ms. Bravo failed to establish by a preponderance of the evidence that the HPV vaccine caused or significantly aggravated her multiple sclerosis.

Consequently, Ms. Bravo's claim for compensation was denied. The decision was made without an evidentiary hearing, as Ms. Bravo had a full opportunity to present her case through expert reports and briefs.

Theory of causation field:
Petitioner Berlin Bravo alleged that the HPV vaccine administered on March 21, 2014, caused or significantly aggravated her multiple sclerosis (MS). The Special Master found that Ms. Bravo likely had undiagnosed MS prior to vaccination, precluding a cause-in-fact claim. For the significant aggravation claim, Ms. Bravo proposed theories of molecular mimicry, persistence of alum causing neurotoxicity, and alum leading to IL-1beta. Petitioner's experts included Dr. Lawrence Steinman and Dr. Yehuda Shoenfeld. Respondent's experts included Dr. Subramaniam Sriram and Dr. Neil Romberg. The Special Master rejected these theories, citing inconsistencies with epidemiological studies (Scheller, Mouchet), the commonness of amino acid similarities without proven biological relevance, and a lack of evidence that attacks on specific proteins would worsen MS. The Special Master also found a lack of a logical sequence of cause and effect and noted the absence of affirmative statements from treating physicians. Temporal association alone was deemed insufficient. The claim was denied by Special Master Christian J. Moran on May 31, 2023. This was an off-Table claim.

Public staged source text:

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DOCUMENT 1: USCOURTS-cofc-1_17-vv-00501-2
Date issued/filed: 2023-06-23
Pages: 36
Docket text: PUBLIC DECISION (Originally filed: 05/31/23) regarding 206 DECISION of Special Master. Signed by Special Master Christian J. Moran. (ceo) Service on parties made.
--------------------------------------------------------------------------------
Case 1:17-vv-00501-EDK Document 207 Filed 06/23/23 Page 1 of 36
* * * * * * * * * * * * * * * * * * * * * *
BERLIN V. BRAVO, *
* No. 17-501V
Petitioner, * Special Master Christian J. Moran
*
v. *
* Filed: May 31, 2023
SECRETARY OF HEALTH *
AND HUMAN SERVICES, *
*
Respondent. *
* * * * * * * * * * * * * * * * * * * * * *
Sol P. Ajalat, Ajalat & Ajalat, LLP, North Hollywood, CA, for petitioner;
Colleen Hartley, United States Dep’t of Justice, Washington, DC, for respondent.
PUBLISHED DECISION DENYING ENTITLEMENT1
Berlin Bravo is claiming that a human papilloma virus (“HPV”) vaccine
either caused her to suffer multiple sclerosis or caused her previously undiagnosed
multiple sclerosis to worsen. The Secretary disputes both claims. Ms. Bravo has
filed a series of reports from experts, of which some do not meaningfully advance
her claims. In contrast, the Secretary has also presented multiple reports from
experts, and these are more persuasive. Similarly, the parties have advocated
through memoranda. Ms. Bravo’s briefs are not effective, and the Secretary’s brief
is convincing. The primary flaw with Ms. Bravo’s evidence is that she has not
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), the
parties have 14 days to identify and move to redact medical or other information, the disclosure
of which would constitute an unwarranted invasion of privacy. Any changes will appear in the
document posted in the website.

Case 1:17-vv-00501-EDK Document 207 Filed 06/23/23 Page 2 of 36
persuasively shown how an HPV vaccination can cause pre-existing multiple
sclerosis to worsen. An independent and second problem is that Ms. Bravo has not
presented a logical sequence of cause and effect showing that the HPV vaccination
harmed her. Accordingly, Ms. Bravo is not entitled to compensation.
Due to the issues raised, the decision is organized unusually. The standards
for adjudication are set forth at the beginning. The next section (Section II)
describes the people whom Ms. Bravo and the Secretary have retained. Section III
starts the analysis by explaining the basis for a finding that Ms. Bravo likely
suffered from multiple sclerosis before she received the third dose of the HPV
vaccine. Section III includes a summary of the procedural history relevant to
determining when Ms. Bravo began to have multiple sclerosis as well as a
summary of the medical records through her initial hospitalization for multiple
sclerosis.2 The analysis continues in Section IV, which resolves whether Ms.
Bravo has presented preponderant proof that the HPV vaccination significantly
aggravated her condition. Within Section IV, parts are devoted to Ms. Bravo’s
more recent medical history, the procedural history regarding a claim that the HPV
vaccination harmed her, and the elements of significant aggravation. The
evaluations in Section III and Section IV are the foundation for a determination
that a hearing is not needed (Section V). Finally, the decision ends with additional
comments (Section VI) and a conclusion (Section VII).
2 The procedural history regarding the gathering of medical records does not affect the
outcome of the case. Therefore, those events are not set forth in this Decision.
Likewise, as Ms. Bravo’s motion for the undersigned’s recusal is irrelevant to the
outcome of her claim, it does not factor into the analysis section of this Decision. However, a
summary is provided here.
Ms. Bravo argued that the undersigned was biased against her and/or her attorney based
on (1) a rescinded March 2, 2020 order requiring Ms. Bravo’s attorney to associate with an
attorney more experienced in the Vaccine Program to assist Ms. Bravo in developing a
significant aggravation claim, and (2) an April 9, 2020 order requiring Ms. Bravo to submit an
affidavit, witnessed by a notary public, in which she affirmed her retention of her attorney as her
counsel of record. Pet’r’s Mot., filed Apr, 27, 2020. The undersigned denied the motion, as it
did not raise any legitimate bases for recusal. All assessments were developed during the course
of the litigation. Order Denying Motion for Recusal, issued May 27, 2020.
On June 12, 2020, Ms. Bravo filed a motion to review the order denying recusal. As the
order was not a final “decision” as defined by the Vaccine Program, Ms. Bravo’s motion was
denied for lack of jurisdiction. Bravo v. Sec'y of Health & Hum. Servs., 149 Fed. Cl. 333, 335
(2020).
2

Case 1:17-vv-00501-EDK Document 207 Filed 06/23/23 Page 3 of 36
I. Standards for Adjudication
A petitioner is required to establish her case by a preponderance of the
evidence. 42 U.S.C. § 300aa–13(1)(a). The preponderance of the evidence standard
requires a “trier of fact to believe that the existence of a fact is more probable than
its nonexistence before [he] may find in favor of the party who has the burden to
persuade the judge of the fact's existence.” Moberly v. Sec'y of Health & Human
Servs., 592 F.3d 1315, 1322 n.2 (Fed. Cir. 2010) (citations omitted). Proof of
medical certainty is not required. Bunting v. Sec'y of Health & Human Servs., 931
F.2d 867, 873 (Fed. Cir. 1991).
Distinguishing between “preponderant evidence” and “medical certainty” is
important because a special master should not impose an evidentiary burden that is
too high. Andreu v. Sec'y of Health & Human Servs., 569 F.3d 1367, 1379-80
(Fed. Cir. 2009) (reversing special master's decision that petitioners were not
entitled to compensation); see also Lampe v. Sec'y of Health & Human Servs., 219
F.3d 1357 (Fed. Cir. 2000); Hodges v. Sec'y of Health & Human Servs., 9 F.3d
958, 961 (Fed. Cir. 1993) (disagreeing with dissenting judge's contention that the
special master confused preponderance of the evidence with medical certainty).
II. People Retained in this Litigation
Ms. Bravo retained a total of five people. The most credible person was a
neuroradiologist, David Wilson. Ms. Bravo also retained two people who have
often expressed opinions that vaccines harmed someone, Lawrence Steinman (a
neurologist with additional qualifications in immunology) and Yehuda Shoenfeld
(an immunologist). Ms. Bravo also submitted reports from two people who have
participated in the Vaccine Program much less frequently, Sin Hang Lee (a
pathologist) and Christopher Shaw, who has earned a Ph.D. and researches
neuroplasticity and neuropathology.
The Secretary has presented reports from three people. Like Ms. Bravo, the
Secretary retained an expert to discuss neuroradiologic studies, Jonathan Kleefield.
Otherwise, to address the claims that the HPV vaccination harmed Ms. Bravo, the
Secretary relied upon two people whom he has often retained. The first is
Subramaniam Sriram, a neurologist with additional qualifications in immunology.
The second is Neil Romberg, an immunologist.
Collectively, the opinions from these people helped understand the issues,
namely, when Ms. Bravo began to suffer from multiple sclerosis and whether the
HPV vaccination contributed to her multiple sclerosis.
3

Case 1:17-vv-00501-EDK Document 207 Filed 06/23/23 Page 4 of 36
III. Part 1: The Evidence Preponderates in Favor of Finding that Ms. Bravo
Suffered from Multiple Sclerosis before the Vaccination
A. Health and Academic Record
Ms. Bravo was born in 1999. The medical records for her approximately
first ten years appear not to contribute to the issues in this case. For more detailed
information, See Pet’r’s Br., filed July 1, 2021, at 10-11 and Resp’t’s Br., filed
March 24, 2022, at 4-5.
When Ms. Bravo was nearly ten years old in 2009, she had problems with
bedwetting, dysuria, incontinence, and constipation. Exhibit 3 at 67, 76. A renal
ultrasound was normal. Id. at 87 (Aug. 20, 2009). A pediatric urologist stated that
Ms. Bravo “holds her urine until it is too late and leaks,” a phenomenon called
“dysfunctional elimination syndrome.” Id. at 108 (Sep. 3, 2009).
In Dr. Sriram’s view, Ms. Bravo’s problems with urination marked an initial
presentation of the multiple sclerosis that was diagnosed years later. Exhibit C at
6-7. However, Dr. Steinman disagreed because urinary tract infections “are not
uncommon in females.” Exhibit 304 at 4.
Dr. Sriram also brought forward Ms. Bravo’s academic record because
“[c]ognitive changes and poor scholastic performance in schools are well
recognized symptomology of [multiple sclerosis].” Exhibit C at 4. Dr. Sririam
presented the following data:
Age Year Grade Language Math Social Studies Science
9 08-09 3 C+ C+ C C+
10 09-10 4 C+ C- B B-
11 10-11 5 C+ C B- B+
12 11-12 6 C F F C-
13 12-13* 7 C- D C- D
14 13-14** 8 F D C- F
4

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Exhibit C at 3; see also Exhibit 5 at 2 (report card from elementary school).
Although Dr. Steinman did not dispute that poor scholastic performance is
associated with multiple sclerosis, he contended that “there are many causes for a
change in scholastic performance.” Exhibit 304 at 5.
The asterisk (*) in the chart reflects that Ms. Bravo received the first and
second doses of the HPV vaccine during the 2012-2013 school year. Ms. Bravo’s
first dose was on October 3, 2012 during a routine “well teen” examination for a
thirteen-year-old. Exhibit 3 at 274-76. She did not report any neurologic problems
during this visit. Id.
The second HPV vaccination was given to Ms. Bravo on May 7, 2013.
Exhibit 3 at 305-06. The context was a medical appointment during which Ms.
Bravo complained about a tender lump on her left jawline, nausea after eating, and
abdominal pain. Id. at 303-06. Ms. Bravo has not asserted that either the first dose
or the second dose of the HPV vaccination harmed her.
The allegedly harmful dose was Ms. Bravo’s third dose of the HPV vaccine,
given during the 2013-2014 school year, marked with two asterisks (**) in the
chart above. The date was March 21, 2014. Exhibit 3 at 370. On that date, she
visited her pediatrician for a another “well teen” visit. Id. at 366. Her gross
neurologic system was “normal by observation.” Id. at 367. She was expected to
return in about one year. Id. at 371.
Any plans for routine medical care were interrupted when Ms. Bravo began
to experience pain in her right eye and intermittently blurry vision in later April
2014. She sought treatment at an emergency department on April 29, 2014.
Exhibit 3 at 1477-79. She was determined to be neurologically intact and
discharged. Id.
The next day, April 30, 2014, she returned to the emergency department and
reported a two-to-three day history of right eye pain and headache. Exhibit 3 at
1481-84. She was directed to seek care from an ophthalmology clinic. Id.
An ophthalmologist determined that Ms. Bravo had difficulty with her vision
and seeing color in her right eye. Exhibit 3 at 384-86 (May 1, 2014). The
ophthalmologist diagnosed her with right retrobulbar neuritis and sent her to the
hospital for an MRI. Id.
The hospitalization lasted from May 1 to May 10, 2014. Exhibit 3 at 1485-
1601. Upon admission, a doctor obtained a history about her eye problems,
consistent with the history recounted above. Id. at 1493. The doctor also
5

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memorialized that Ms. Bravo “had a HPV vaccine 1 mo ago.” Id. The doctor
sought a consultation with a neurologist and ordered an MRI. Id. at 1497. The
doctor was concerned that Ms. Bravo might suffer from a
“demyelinating/autoimmune process (MS given female and age vs. ADEM.)” Id.
at 1496.
The MRI, which presents critical information about when Ms. Bravo began
to have lesions in her brain, was performed on May 2, 2014. The MRI revealed
“5-10 scattered supratentorial areas of T2 signal hyperintensity within the white
matter along the callosal-septal interface.” Exhibit 3 at 1504. Some of the lesions
did not enhance on contrast. Id. at 1583. As discussed below, experts retained in
the litigation were provided the MRI images and commented upon them
extensively.
By May 8, 2014, Ms. Bravo’s doctors thought multiple sclerosis was likely.
Exhibit 3 at 1574. This diagnosis was confirmed the next day.3 Id. at 1583. She
was treated with intravenous steroids, oral steroids, and plasmapheresis. She was
discharged on May 10, 2014. Id. at 1593.
B. Procedural History regarding the Preexistence of Multiple
Sclerosis
In his first report, Dr. Sriram opined that Ms. Bravo suffered from multiple
sclerosis as early as 2008, based upon Ms. Bravo’s dysuria, incontinence, and
constipation. Exhibit C at 6. Dr. Sriram also relied upon imaging from Ms.
Bravo’s May 2, 2014 MRI. Exhibit C at 7-10.
After Dr. Sriram opined that Ms. Bravo suffered from multiple sclerosis
before the vaccination, the parties discussed the viability of a significant
3 Petitioner states that it is “a fundamental error” to base the analysis “on an agreed and
uncontested medical diagnosis . . . of multiple sclerosis,” because “[s]uch a diagnosis is rendered
for purposes of [determining] methods of treatment of the existing disease process and not for
determining the original etiological cause of the disease.” Pet’r’s Br. at 5. Petitioner further
argues that “the actual basic underlying disease process from which [she] is suffering is a
heterogenous auto-immune disease process which, when analyzed, presents with all of the
disease process elements. Focusing the decision making process on multiple sclerosis may, and
likely does, contribute to an erroneous determination of what was the nature of the original
etiological agent of the scaring in the left side of [her] brain.” Id. However, in both the original
petition (filed April 10, 2017) and amended petition (filed November 16, 2018), petitioner
alleged that she suffers “a cause in fact injury consisting of demyelinating disease process(s)
known as optic neuritis and multiple sclerosis.”
6

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aggravation claim in a series of status conferences. After a discussion in an
October 15, 2018 status conference, Ms. Bravo added a significant aggravation
claim. Am. Pet., filed Nov. 16, 2018. However, Ms. Bravo did not present any
evidence regarding significant aggravation, and counsel for petitioner maintained
that the primary claim was for causation, and that the multiple sclerosis did not
exist before the vaccination. See Order, issued July 29, 2019.
On January 23, 2020, the undersigned issued an order for briefs addressing
whether Ms. Bravo suffered from multiple sclerosis before vaccination, noting that
Ms. Bravo had not yet filed evidence on significant aggravation, and finding that
she was thus pursuing a causation-in-fact claim only. Order, issued Jan. 23, 2020
at 7 n.4.
A status conference was held on February 6, 2020 to review the order.
During the status conference, petitioner indicated that she wanted to proceed on a
significant aggravation claim. See Order, issued Feb. 10, 2020. Ms. Bravo
requested an opportunity to retain a neuroradiologist. Pet’r’s Status Rep., filed
Feb. 25, 2020. The Secretary did not oppose allowing Ms. Bravo “a final
opportunity.” Resp’t’s Status Rep., filed May 8, 2020.
The parties provided images of Ms. Bravo’s MRIs to their experts in
radiology and neuroradiology. For Ms. Bravo, Dr. Wilson wrote two reports.
Exhibits 369 and 394. Dr. Steinman added a short report. Exhibit 400. For the
Secretary, Dr. Kleefield wrote a report (Exhibit N) and Dr. Sriram wrote another
report (Exhibit M).
After reviewing the evidence, the undersigned found that the evidence
preponderated in favor of finding that a lesion detected in Ms. Bravo’s brain was
so old that it must have developed before she was vaccinated. This lesion was an
unrecognized sign of multiple sclerosis. Thus, Ms. Bravo suffered from
undiagnosed multiple sclerosis before the vaccination. Tentative Finding, issued
Mar. 26, 2021.
After the Tentative Finding, the parties have not submitted any additional
evidence regarding the onset of Ms. Bravo’s multiple sclerosis. Nevertheless, Ms.
Bravo challenges the Tentative Finding.
C. Analysis
Ms. Bravo’s objections to the Tentative Finding can be placed into two
categories. The first is procedural and the second is evidentiary.
7

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1. Procedural
Ms. Bravo argues that special masters must base findings upon the entire
record. Pet’r’s Br. at 8. Although Ms. Bravo does not cite any authority for this
proposition, the Vaccine Act says as much: special masters are to resolve cases
based “on the record as a whole.” 42 U.S.C. § 300aa–13(a)(1).
In this context, Ms. Bravo maintains “expert medical witness opinion
testimony is required.” Pet’r’s Br. at 8. Although unstated, Ms. Bravo seems to be
arguing that oral testimony is required. If this is Ms. Bravo’s argument, then it is
mistaken. Special masters may resolve entire cases without holding a hearing.
Kreizenbeck v. Sec’y of Health & Hum. Servs., 945 F.3d 1362, 1365 (Fed. Cir.
2020). In doing so, special masters must consider the relevant evidence. Mager v.
Sec’y of Health & Hum. Servs., 158 Fed. Cl. 136, 154 (2022). Here, the
undersigned has considered all the evidence. Ms. Bravo’s briefs filed after the
Tentative Finding appear not to suggest that the undersigned overlooked any
evidence. Instead, Ms. Bravo seems to be challenging the weight given to that
evidence. This brings up Ms. Bravo’s second objection to the Tentative Finding.
2. Evidentiary
In some respects, the evidence regarding the onset of Ms. Bravo’s multiple
sclerosis is confusing. But, in other and more important respects, the evidence is
simple.
The confusing part derives from the report of Dr. Wilson. From Dr.
Wilson’s review of Ms. Bravo’s original MRI images, he presented three examples
of “acute demyelinating injury” in his Figure 1. Exhibit 369 at 3. Dr. Wilson also
presented in his Figure 2 characteristics of the five largest lesions from Ms.
Bravo’s May 1, 2014 MRI. Id. at 4. However, Dr. Wilson does not state that the
three lesions in Figure 1 correspond to the five lesions in Figure 2. See id.
In responding to Dr. Wilson, Dr. Kleefield asserts one of the three images in
Figure 1 is an “artifact.” Exhibit N at 3. But, Dr. Wilson maintained his position
that the enhancement is “real.” Exhibit 394 at 2-3.
To argue against the Tentative Finding, Ms. Bravo relies (in part) upon Dr.
Kleefield’s opinion regarding the “artifact.” Pet’r’s Br. at 7 and 9. In citing the
opinion of the Secretary’s expert, Ms. Bravo overlooks her own expert’s argument
that the image Dr. Wilson presented in Figure 1 shows an artifact. Exhibit 394 at 3
(Dr. Wilson: “I disagree with [Dr. Kleefield] that this lesion is artifactual.”).
8

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In any event, the three enhancements from Dr. Wilson’s Figure 1 are not
relevant. The key material is found in Dr. Wilson’s Figure 2.
In Figure 2, Dr. Wilson identifies two lesions that lack enhancement.
Exhibit 369 at 4; see also Exhibit M at 2 (Dr. Sriram: “Dr. Wilson ‘states that there
were 2 non-enhancing lesions seen on the MRI on 5/2/2014’”). These two non-
enhancing lesions make the issue relatively easy. Dr. Sriram explained that one of
the lesions, which can be described as being in the left frontal region or
juxtacortical region, is a “hypo intense lesion” called a black hole. Exhibit M at 3;
see also Exhibit N at 3-4; Frantz v. Sec’y of Health & Hum. Servs., No. 13-158V,
2019 WL 3713942, at *17 (Fed. Cl. Spec. Mstr. June 24, 2019) (discussing black
holes), mot. for rev. denied, 146 Fed. Cl. 137 (2019). Due to the way black holes
are created, the lesion must have existed before the vaccination. Exhibit M at 3-6.
On this point, Dr. Wilson agrees. Exhibit 369 at 7; see also Exhibit 394 at 3 (Dr.
Wilson stating “There is not major disagreement among experts in this case re: the
chronicity of the discussed juxtacortical lesion”).
With respect to the first of two non-enhanced lesions, Dr. Wilson is left in a
challenging position. Having admitted the lesion pre-existed the vaccination, Dr.
Wilson maintains the lesion is not related to multiple sclerosis. See Exhibit 369 at
4-5 and 7. This argument is difficult to sustain. Dr. Wilson states: “Juxtacortical
lesions are seen in MS and may even be characteristic of MS.” Exhibit 394 at 3.
This statement aligns with Dr. Sriram’s view. Exhibit M at 3-6.
Moreover, Dr. Sriram identifies a “weakly enhancing lesion in the left
occipital trigone.” Exhibit M at 9. Dr. Sriram also asserted that this lesion likely
preexisted the vaccination due to its size (volume). Exhibit M at 7-8. Dr. Wilson
does not meaningfully engage with Dr. Sriram on this point. See Exhibit 394 at 4.
Dr. Wilson states “there is no definitive MRI evidence that demyelinating
disease preceded vaccination on 3/21/2014.” Exhibit 394 at 1; see also Exhibit 369
at 6. The evidence probably is not “definitive.” It might be a possibility that
before the vaccination, Ms. Bravo could have had a lesion in her brain that was
entirely separate from multiple sclerosis. However, the burden of proof is not
“definitiveness.” It is only preponderance. As Dr. Kleefield explained: “no one
disagrees that the overwhelming majority of the lesions seen on MRI scans are
typical for demyelinating disease. Therefore, such a diagnosis should also apply to
the left frontal subcortical lesion, whose signal characteristics indicate it is a
chronic abnormality preceding the vaccination date in question.” Exhibit N at 4.
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In addition to radiologic information about Ms. Bravo from her MRIs, other
evidence supports a finding that she was, more likely than not, suffering from
multiple sclerosis before vaccination. Dr. Sriram identified clinical and academic
problems. Exhibit C at 6-7; see also Resp’t’s Br. at 5 n.9.4 Dr. Steinman
responded. Exhibit 304 at 4-5. As previously stated, this evidence is “not clear-
cut.” Tentative Finding at 2.5
3. Summary
The Tentative Finding cited two cases in which the (undersigned) special
master found lesions pre-existed a vaccination. Tentative Finding at 2, citing W.C.
v. Sec’y of Health & Hum. Servs., No. 07-456V, 2011 WL 4537877 (Fed. Cl.
Spec. Mstr. Feb. 22, 2011), mot. for rev. denied in relevant part, 100 Fed. Cl. 440,
451-53 (2011), aff’d, 704 F.3d 1352 (Fed. Cir. 2013); Frantz v. Sec’y of Health &
Hum. Servs., No. 13-158V, 2019 WL 3713942, at *17 (Fed. Cl. Spec. Mstr. June
24, 2019) (discussing black holes), mot. for rev. denied, 146 Fed. Cl. 137 (2019).
Of this pair, W.C. carries the most weight due to the Federal Circuit’s affirmance.
Other special masters have reached similar results. Maciel v. Sec’y of
Health & Hum. Servs., No. 15-362V, 2018 WL 6259230, at *24 (Fed. Cl. Spec.
Mstr. Oct. 12, 2018); L.Z v. Sec’y of Health & Hum. Servs., No. 14-920V, 2018
WL 5784525, at *17 (Fed. Cl. Spec. Mstr. Aug. 24, 2018). Ms. Bravo fails to
address any of these precedents, including the two cases identified in the Tentative
Finding.
Accordingly, to the extent required, the undersigned confirms the finding,
which was tentative. A preponderance of the evidence supports the finding that
Ms. Bravo had undiagnosed multiple sclerosis before the vaccination.
Consequently, Ms. Bravo cannot prevail on a theory that the HPV vaccination was
the cause-in-fact of her multiple sclerosis. Locane v. Sec’y of Health & Hum.
Servs., 685 F.3d 1375, 1380-81 (Fed. Cir. 2012). She can, however, advance a
claim that the HPV vaccination significantly aggravated the multiple sclerosis. As
4 Dr. Sriram’s opinion contradicts Ms. Bravo’s assertion that in “unanimous agreement of
the expert witnesses, [Ms. Bravo] was healthy with no clinical signs and symptoms of… multiple
sclerosis.” Pet’r’s Br. at 11.
5 Dr. Wilson’s critiques of Dr. Sriram’s assessment of the clinical picture in Ms. Bravo’s
case, Exhibit 369 at 6, are off base. As Dr. Wilson explained, neuroradiologists like him
typically defer to practicing neurologists. Id.; see also Exhibit N at 1.
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Dr. Wilson stated, “the immune challenge of a vaccine can worsen disease.”
Exhibit 394 at 3. That question is addressed next.
IV. Part 2 : The Evidence Does Not Preponderate in Favor of Finding the
HPV Vaccine Significantly Aggravated Ms. Bravo’s Multiple Sclerosis
A. Health
Ms. Bravo’s health before her diagnosis with multiple sclerosis was set out
above in section III.A. Following the third HPV vaccination, the parties basically
agree about Ms. Bravo’s health. See Pet’r’s Br. at 21-23; Resp’t’s Br. at 7-10.
Once diagnosed with multiple sclerosis, Ms. Bravo explored a variety of
treatments. During a relapse in July 2014, Ms. Bravo was tested for an infection
with the Epstein-Barr virus. The results indicated that Ms. Bravo had a past
infection. Exhibit 3 at 1374. Much later in the litigation, Dr. Romberg opined that
the infection with the Epstein-Barr virus was a better explanation for why she
developed multiple sclerosis. Exhibit V. In response, Dr. Steinman maintained
that an infection with the Epstein-Barr virus was necessary but not sufficient to
cause multiple sclerosis. Exhibit 427.
Otherwise, the remaining medical records seem not to inform the issue of
whether the HPV vaccination worsened Ms. Bravo’s multiple sclerosis. See
Pet’r’s Br. at 23 (summarizing two and half years of medical records in two
paragraphs). Thus, they are not written about here, although those recent medical
records have been considered.
B. Procedural History
Setting aside Dr. Wilson, whose role was to comment on radiologic
evidence, Ms. Bravo presented reports from four people. These are: Dr. Steinman,
Dr. Shoenfeld, Dr. Lee, and Dr. Shaw. The Secretary filed reports from Dr. Sriram
and Dr. Romberg, again excepting the neuroradiologist (Dr. Kleefield).
1. Dr. Shaw and Dr. Lee
It appears that Ms. Bravo is relying upon Dr. Steinman and Dr. Shoenfeld
exclusively and not relying upon either Dr. Lee or Dr. Shaw. Other than a
discussion of the qualifications of Dr. Lee and Dr. Shaw, Ms. Bravo does not
advance their opinions. See Pet’r’s Br. at 18-19. The Secretary also understood
that Ms. Bravo was not relying upon opinions from either Dr. Lee or Dr. Shaw.
Resp’t’s Br. at 24 n.24. Ms. Bravo, in turn, did not correct any misunderstanding
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or otherwise argue for opinions from Dr. Lee or Dr. Shaw. See Pet’r’s Reply, filed
April 8, 2022 and Pet’r’s Supplemental Reply, filed May 4, 2022.
Nevertheless, if only to confirm that Dr. Shaw’s and Dr. Lee’s opinions have
been considered, they are addressed briefly.
a) Dr. Lee
Dr. Lee wrote four reports, which were filed as Exhibits 92, 251, 325 and
352. A fifth report (Exhibit 166) revised Dr. Lee’s original report (Exhibit 92). In
his final two reports, Dr. Lee addressed, among other topics, an epidemiological
study by Scheller. Exhibits 325, 352.
A general thrust of Dr. Lee’s opinion is that the HPV vaccine acts as a TLR9
agonist and that TLR9 activates cells of the innate immune system to cause
multiple sclerosis. See, e.g., Exhibit 251 at 9, 30. Dr. Lee contends that the HPV
vaccines “contain a significant quantity” of HPV DNA fragments bound to
amorphous aluminum hydroxyphosphate sulfate (“AAHS”), acting as a “silent
TLR9 agonist.” Id. at 28. However, as previously stated, it appears that Ms. Bravo
is not advancing this theory because, at best, she quoted one paragraph of one
report from Dr. Lee in her brief. Pet’r’s Br. at 19. This limited quotation does not
comply with the requirement that the parties should not simply quote from an
expert’s report. Order for Briefs, filed March 26, 2021, at 6.
In any event, Dr. Romberg has undermined the persuasive value of a theory
based upon TLR9 in his reports. Dr. Romberg points out that the Zannetti study,6
which Dr. Lee cites, does not prove that the HPV vaccine is a TLR9 agonist, but
rather, suggests that a significant portion of the activating effect is unrelated to
TLR9 activation. Exhibit F at 2. Dr. Romberg further notes that Dr. Lee’s
estimate that “a significant quantity” of HPV DNA is bound by AAHS is not a
quantitative estimate, and is based only on Dr. Lee’s own experiments using a
technique which cannot quantitate DNA. Id. at 2-3. “[I]n summary . . . both the
quantity of DNA in Gardasil and its ability to activate TLR9 remain fully in
question.” Id.; see also Exhibit H at 1-2. Moreover, one special master
persuasively found that Dr. Lee’s presentation of a TLR9 theory was not
persuasive. E.S. v. Sec’y of Health & Hum. Servs., No. 17-480V, 2020 WL
9076620, at *50 (Fed. Cl. Spec. Mstr. Nov. 13, 2020) (noting that Dr. Lee had not
presented any persuasive or reliable literature, but had “only proposed that general
research he had performed was enough.”), mot. for rev. denied, 154 Fed. Cl. 149
6 Bibliographic information for the articles cited in this decision is found in the appendix.
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(2021); c.f. Aviles v. Blasio, No. 20 Civ. 9829, 2021 WL 796033, at *14 (S.D.N.Y.
Mar. 2, 2021) (describing one of Dr. Lee’s opinions as “rank speculation”).
Under these circumstances an extended discussion of Dr. Lee’s background
and his opinions is unnecessary. It suffices to state that they are not persuasive.
Cf. Roane v. McDonough, 64 F.4th 1306, 1309 (Fed. Cir. 2023) (explaining that
the Board of Veterans’ Appeals is not required to explain how each piece of
evidence factored into its decision).
b) Dr. Shaw
Dr. Shaw drafted three reports. Exhibits 30, 132 (one-page), and 296. He
appears to be asserting that Ms. Bravo’s case represents an example of an
Autoimmune Syndrome Induced by Adjuvants (“ASIA”).
Ms. Bravo pays even less attention to reports from Dr. Shaw. She did not
quote his report or otherwise cite to them. At best, Ms. Bravo references the ASIA
theory in the context of Dr. Shoenfeld. Pet’r’s Br. at 12.
Accordingly, it appears that the reports from Dr. Shaw carry little, if any,
independent weight. To the extent that Dr. Shaw is asserting ASIA, special
masters have consistently rejected ASIA. See, e.g., Rowan v. Sec’y of Health &
Hum. Servs., 2015 WL 3562409 (Fed. Cl. May 18, 2015) (denying motion for
review and ruling special master did not err in not crediting ASIA); Phillips v.
Sec’y of Health & Hum. Servs., No. 16-906V, 2020 WL 7767511 (Fed. Cl. Spec.
Mstr. Nov. 23, 2020); Pearson v. Sec’y of Health & Hum. Servs., No. 16-9V, 2019
WL 3852633 (Fed. Cl. Spec. Mstr. July 31, 2019). The undersigned agrees with
the reasoning in these cases, and Ms. Bravo has presented no reason—let alone a
persuasive reason—for reconsidering those outcomes. See Pet’r’s Supp’l Br. at 3.
To the extent that Dr. Shaw is supporting Dr. Shoenfeld’s opinions, Dr. Shaw’s
work is considered in the context of Dr. Shoenfeld.
2. Dr. Shoenfeld
Unlike the situation for Dr. Lee and Dr. Shaw, in which Ms. Bravo appears
to have disclaimed any reliance upon them, Ms. Bravo is certainly putting forward
the opinions of Dr. Shoenfeld. Thus, the disclosure of Dr. Shoenfeld’s opinions
and the Secretary’s responses to those opinions are discussed in more detail.
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Dr. Shoenfeld’s First Report. Dr. Shoenfeld’s first report is fourteen pages
plus an additional page listing 19 references. Exhibit 9.7 After some preliminary
matters, including a review of his qualifications and the facts of Ms. Bravo’s case,
Dr. Shoenfeld discussed a few case reports in which the HPV vaccine preceded the
development of a different autoimmune disease, neuromyelitis optica (“NMO”).
Id. at 7-10.
For theories by which the HPV vaccine can cause harmful consequences, Dr.
Shoenfeld offered two possibilities. First, Dr. Shoenfeld emphasized that the
adjuvant for the HPV vaccine could persist leading to “delayed neurotoxicity.” Id.
at 10. In this context, Dr. Shoenfeld explained that aluminum has been found in a
condition known as macrophagic myofasciitis. Id. at 10-11. Second, Dr.
Shoenfeld suggested that the adjuvant could augment a reaction driven by
molecular mimicry as Dr. Steinman has proposed. Id. at 11-12.
Dr. Shoenfeld’s Second Report. In response to an order seeking clarification
from Dr. Shoenfeld, Dr. Shoenfeld wrote a second report, which is dated February
5, 2018, and filed as Exhibit 142. He stated that aluminum is associated with
demyelinating diseases and aluminum can accumulate in the brain. Exhibit 142 at
2-3.
Dr. Romberg’s First Report. Dr. Romberg opined that, based upon an
epidemiologic study (Scheller), the HPV vaccine was unlikely to cause or to
worsen multiple sclerosis. Exhibit A at 14. In response to Dr. Shaw, Dr. Romberg
presented information about the hemodialysis of aluminum and the amount of
aluminum contained in an HPV vaccine. Id. at 15. Dr. Romberg disputed the
potential harmful nature of aluminum by citing a large epidemiologic study
(Linneberg). Id.
Dr. Sriram’s First Report. Dr. Sriram maintained that the case reports on
NMO did not inform the question of multiple sclerosis. Exhibit C at 11. Dr.
Sriram also noted that one of the studies Dr. Shoenfeld had cited (referenced by
Dr. Shoenfeld as the study by “Brocke and colleagues” but cited as Ufret-Vincenty
et al., Exhibit 9 at 12, 15) was not about the HPV vaccine, but was about the
Epstein-Barr virus. Id. at 12. Finally, Dr. Sriram opined that no evidence shows
aluminum in vaccines causes multiple sclerosis. Id. at 13.
7 This first report was essentially refiled as Exhibit 324. See CM/ECF 72.
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Dr. Shoenfeld’s Third Report. In Dr. Shoenfeld’s third report, he briefly
responded to Dr. Romberg’s citation to the Scheller epidemiologic study. Exhibit
311.
Dr. Shoenfeld’s Fourth Report. Dr. Shoenfeld responded to Dr. Sriram’s
report by extending his discussion of molecular mimicry and Kanduc. Exhibit 314
at 3-5.8 Dr. Shoenfeld offered the idea that multiple sclerosis could be aggravated
due to hyper-stimulation of the immune system by the HPV vaccine. Id. at 5
(citing, among other articles, a 2009 article by Kanduc and a 2016 article by
Kanduc and Shoenfeld).
Dr. Romberg’s Second Report. This report did not direct any comments to
Dr. Shoenfeld. However, with respect to the issue of aluminum toxicity raised by
Dr. Shaw, Dr. Romberg again cited the Danish study. Exhibit F at 6.
Dr. Sriram’s Second Report. Dr. Sriram continued to disagree with Dr.
Shoenfeld’s reliance on case reports involving demyelinating diseases other than
multiple sclerosis because, in Dr. Sriram’s view, demyelinating diseases have
different etiologies. Exhibit G at 6.
Dr. Shoenfeld’s Fifth and Sixth Reports. Dr. Shoenfeld’s fifth report
generally concerned the question of onset. Exhibit 342.
In his sixth report, Dr. Shoenfeld responded to Dr. Romberg’s preference for
looking at epidemiologic studies by highlighting the need to look at animal models.
Exhibit 344 at 1. In this context, Dr. Shoenfeld cited an article by Inbar, which
was filed as Exhibit 346.
3. Dr. Steinman
Like Dr. Shoenfeld, Dr. Steinman wrote a series of reports to which Dr.
Sriram and Dr. Romberg responded. A summary of their respective positions is as
follows:
Dr. Steinman’s First Report. Dr. Steinman began his first report with a
summary of his qualifications and a recitation of Ms. Bravo’s medical history.
Exhibit 70 at 1-7. Dr. Steinman then proposed two different theories by which an
HPV vaccination might affect multiple sclerosis. The first theory is molecular
8 Dr. Shoenfeld and Dr. Sriram also debated the onset of Ms. Bravo’s multiple sclerosis.
Because the previous section resolved this issue, these exchanges are not detailed here.
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mimicry based upon BLAST searches. Id. at 8-20. Dr. Steinman conducted these
BLAST searches despite not knowing the dominant antigen associated with
multiple sclerosis. See id. at 8-10. The second theory involves alum9 and was
presented in approximately two paragraphs. Id. at 20. His section on timing
(section 6) was based upon an assertion that the HPV vaccine caused Ms. Bravo’s
multiple sclerosis. Id. at 20-21. Dr. Steinman did not state when the multiple
sclerosis began. See id. at 22. Finally, in the section on the logical sequence of
cause and effect (section 7), Dr. Steinman did not say anything about Ms. Bravo.
Id. at 22.
Dr. Steinman’s Second Report. In response to a February 27, 2018 order,
Dr. Steinman presented additional support for his theory involving alum. Dr.
Steinman asserted that alum adjuvants induce a cytokine, known as IL-1beta. IL-
1beta, according to Dr. Steinman, “has a critical role in the pathogenesis of
[multiple sclerosis].” Exhibit 133 at 5.
Dr. Romberg’s First Report. In addressing Dr. Lee’s opinions, Dr. Romberg
cited the Scheller epidemiologic study. Exhibit A at 10-11. Dr. Romberg also
addressed Dr. Steinman’s alum theory and his molecular mimicry theory. Id. at 12.
Dr. Sriram’s First Report. Although Dr. Steinman’s BLAST searches
involved myelin basic protein and myelin oligodendrocyte-glycoprotein, Dr.
Sriram maintained that those substances have not been implicated in the pathology
of multiple sclerosis. Exhibit C at 13.
Dr. Steinman’s Third Report. Dr. Steinman responded to both Dr. Romberg
and Dr. Sriram in a single report. For Dr. Romberg, Dr. Steinman asserted that
alum in the vaccine boosts the response from the immune system. Exhibit 304 at
1. For Dr. Sriram, Dr. Steinman argued that Ms. Bravo must have some genetic
susceptibility to developing an adverse reaction to the HPV vaccine. Id. at 4.10
9 Alum is short for “aluminum adjuvants,” and is a component in the Gardasil vaccine.
Exhibit 133 at 1; see also Gross v. Sec'y of Health & Hum. Servs., No. 17-1075V, 2022 WL
9669651, at *17 n.59 (Fed. Cl. Sept. 22, 2022).
10 As with Dr. Shoenfeld, Dr. Steinman also contributed opinions as to when Ms. Bravo
began suffering from multiple sclerosis. See, e.g., Exhibit 304 at 5-6. But, again, the details are
omitted from this discussion on significant aggravation.
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Dr. Romberg’s Second Report. Dr. Romberg argued that the HPV virus
evades detection from the immune system. Thus, alum does not boost the immune
response. Exhibit F at 7-8.
Dr. Steinman’s Fourth Report. To support his theory involving molecular
mimicry, Dr. Steinman relied upon information he gained from consulting the
immune epitope database. Exhibit 349 at 2-8. Dr. Steinman also proposed that
Ms. Bravo might establish the HPV vaccine significantly aggravated her multiple
sclerosis. Id. at 12. In the context of reviewing the six Loving prongs, Dr.
Steinman’s section about the logical sequence of cause and effect was one
sentence. Id. at 13.
Dr. Romberg’s Third Report. Dr. Romberg disagreed with how Dr.
Steinman was using the immune epitope database. Exhibit H at 3. Also, in the
context of responding to Dr. Lee, Dr. Romberg cited another epidemiologic study,
Klein. Id.
Dr. Steinman’s Sixth Report.11 In the briefing stage, Dr. Steinman
presented two new papers (by Robinson & Steinman and Lanz et al.) about the
potential role of Epstein-Barr viruses causing multiple sclerosis. Exhibit 414,
dated April 29, 2022.
Dr. Romberg’s Fourth Report. Based upon Dr. Steinman’s most recent
report, Dr. Romberg proposed that an Epstein-Barr infection was a better
explanation for Ms. Bravo’s multiple sclerosis. Exhibit V.
Dr. Steinman’s Seventh Report. Dr. Steinman asserted that the recent
studies indicate that an infection with Epstein-Barr virus is necessary, but not
sufficient, to cause multiple sclerosis. Another factor is needed and in Ms. Bravo’s
case the additional factor was the HPV vaccination. Exhibit 427.
C. Elements of Significant Aggravation
As confirmed in W.C. v. Sec'y of Health & Human Servs., 704 F.3d 1352,
1357 (Fed. Cir. 2013), the elements of an off-Table significant aggravation case
were stated in Loving. There, the Court blended the test from Althen v. Sec'y of
Health & Human Servs., 418 F.3d 1274, 1279 (Fed. Cir. 2005), which defines off-
Table causation cases, with a test from Whitecotton v. Sec'y of Health & Human
11 Dr. Steinman's fifth report commented on the reports submitted by neuroradiologists
after reviewing Ms. Bravo’s MRIs. Exhibit 400.
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Servs., 81 F.3d 1099, 1107 (Fed. Cir. 1996), which concerns on-Table significant
aggravation cases. The resulting test has six components. These are:
(1) the person's condition prior to administration of the vaccine, (2) the
person's current condition (or the condition following the vaccination if that
is also pertinent), (3) whether the person's current condition constitutes a
“significant aggravation” of the person's condition prior to vaccination, (4) a
medical theory causally connecting such a significantly worsened condition
to the vaccination, (5) a logical sequence of cause and effect showing that
the vaccination was the reason for the significant aggravation, and (6) a
showing of a proximate temporal relationship between the vaccination and
the significant aggravation.
Loving, 86 Fed. Cl. at 144.
D. Analysis
In resolving claims of significant aggravation, special masters may focus
their analysis on the last three prongs of the Loving test, which correspond to the
traditional Althen factors. Walker v. Sec’y of Health & Hum. Servs., No. 18-
299V, 2022 WL 11141194, at *3 (Fed. Cl. Spec. Mstr. Sep. 27, 2022) (citing
Hennessey v. Sec’y of Health & Hum. Servs., No. 01-190V, 2009 WL 1709053, at
*42 (Fed. Cl. Spec. Mstr. May 29, 2009), mot. for rev. denied, 91 Fed. Cl. 126
(2010)).
1. Loving Prong 4 / Althen Prong 1
Ms. Bravo’s burden is to present a reliable and persuasive medical theory.
Faup v. Sec’y of Health & Hum. Servs., 147 Fed. Cl. 445, 459 (2019) (citing
Boatmon v. Sec’y of Health & Hum. Servs., 941 F.3d 1351, 1360 (Fed. Cir. 2019)
and Knudsen v. Sec’y of Health & Hum. Servs., 35 F.3d 543, 548 (Fed. Cir.
1994)). The Secretary may controvert the evidence Ms. Bravo submits. de Bazan
v. Sec'y of Health & Hum. Servs., 539 F.3d 1347, 1353–54 (Fed. Cir. 2008).
When the Secretary challenges a petitioner’s Althen prong one evidence, a
special master is not required to find the petitioner automatically has met the
burden regarding a causal theory. M.S.B. by Bast v. Sec’y of Health & Hum.
Servs., 117 Fed. Cl. 104, 123 (2014) (ruling special master was not arbitrary in
rejecting a theory of oxidative stress and noting that the Federal Circuit has
determined the special masters are responsible for assessing “conflicting testimony
of expert witnesses in determining whether a reputable theory has been proven”),
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appeal dismissed, 579 Fed. App’x 1001 (Fed. Cir. 2014); Spates v. Sec’y of Health
& Hum. Servs., 76 Fed. Cl. 678, 684 (2007).
As explained above, Ms. Bravo maintains that she is putting forward two
theories. “There are two generally accepted medical theories as to the original
etiological cause of an autoimmune disease due to [an HPV vaccination]. . . . One
is the mimicry theory and the second is the ASIA theory developed by Petitioner’s
expert witness Dr. Yehuda Shoenfeld.” Pet’r’s Br. at 12. Ms. Bravo elaborates:
“The two theories are essentially the same with ASIA in name identifying the
specific causal factor as an adjuvant.” Id.
However, Ms. Bravo’s characterization of her experts’ theories is mistaken.
Dr. Shoenfeld proposes that alum accumulates in the brain and causes
neurotoxicity. Exhibit 9 at 10-11; Exhibit 142 at 3. In these reports, Dr. Shoenfeld
does not discuss any cytokines and he does not talk about IL-1beta. In contrast,
Dr. Steinman proposes that alum leads to a creation of and/or activation of IL-
1beta and IL-1beta leads to multiple sclerosis. Exhibit 133 at 5. Dr. Steinman
does not assert that alum persists. Thus, although Dr. Shoenfeld and Dr. Steinman
propose theories that start with alum, each theory proceeds differently.
To be sure, Dr. Steinman and Dr. Shoenfeld slightly overlap with respect to
the remaining theory, molecular mimicry. Dr. Steinman proposes that certain
sequences of amino acids in the HPV vaccine resemble (or mimic) sequences of
amino acids in proteins of the nervous system, myelin basic protein and myelin
oligodendrocyte-glycoprotein. Exhibit 70 at 10. Dr. Shoenfeld, but not Dr.
Steinman, adds that the alum in the HPV vaccination can hyper-stimulate the
immune system. Exhibit 314 at 5. At no point did Dr. Steinman assert that the
part of the HPV vaccine that serves as the foundation for his theory of molecular
mimicry is found in the adjuvant.
Accordingly, three theories are evaluated below. They are the persistence of
alum causing neurotoxicity, alum leading to IL-1beta, and molecular mimicry.
Because Ms. Bravo devotes most attention to molecular mimicry, see Pet’r’s Br. at
12-13; Pet’r’s Supp’l Br. at 3-5, and Pet’r’s Reply at 4-5; that theory is considered
most extensively. Before those individual theories are detailed, an assessment of
the epidemiologic evidence the Secretary submitted begins the overall analysis.
a) Epidemiology
Epidemiology is a method by which medical researchers determine whether
an exposure to a substance changes the incidence of a condition. For example,
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when Dr. Steinman was assisting this country on a committee in evaluating
whether veterans who served in the Gulf War developed various diseases at higher
rates, Dr. Steinman and other committee members considered whether
epidemiologic evidence would be useful. Exhibit 72. For a lengthy discussion of
the value of epidemiologic studies in the Vaccine Program, see Tullio v. Sec’y of
Health & Human Servs., No. 15-51V, 2019 WL 7580149, at *5-8 (Fed. Cl. Spec.
Mstr. Dec. 19, 2019), mot. for rev. denied, 149 Fed. Cl. 448, 475 (2020); see also
P.M. v. Sec’y of Health & Hum. Servs., No. 16-949V, 2019 WL 5608859, at *24-
25 (Fed. Cl. Spec. Mstr. Sep. 24, 2019) (finding that epidemiologic studies
weighed against finding the flu vaccine can worsen multiple sclerosis).
Among the hundreds of articles filed, two epidemiologic studies stand out
and a third merits some discussion. The first is by Nikolai Madrid Scheller and
others. Exhibit A-12. The second is by Julie Mouchet and others. Exhibit C-4.
The third is by Nicola Klein and others. Exhibit H-2.
The Scheller group “conducted a cohort study of all Danish and Swedish
girls and women aged 10 years to 44 years on the basis of nationwide registers and
investigated the risk of multiple sclerosis and other demyelinating diseases …
following qHPV vaccination.” Scheller at 55.12 The study involved nearly four
million females, among whom 789,082 people received nearly two million doses
of the vaccine. Because multiple sclerosis may have an insidious onset, the
researchers considered a “2-year (730 days) risk period following the latest qHPV
vaccination.” Id. at 56. The researchers found that the adjusted risk ratio was 1.01
with a 95% confidence interval of 0.76-1.34. Id. at 59. They concluded that
“qHPV vaccination, among girls and women, was not associated with the
development of multiple sclerosis” and their findings “do not support concerns
about a causal relationship between qHPV vaccination and demyelinating
diseases.” Id. at 60.
The Scheller study was incorporated into the Mouchet analysis, which is the
second important epidemiologic study. Mouchet and colleagues conducted a meta-
analysis of studies involving the HPV vaccine and various demyelinating diseases,
including multiple sclerosis. For multiple sclerosis, the investigator evaluated six
studies (including Scheller, which is reference 42 in the Mouchet article).
Mouchet at 114. The number of people receiving a vaccination in the pooled
group exceeded two million, with the Scheller article contributing approximately
12 The qHPV vaccine analyzed in Scheller is the same vaccine that Ms. Bravo received.
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half. Id. at 115 (Fig. 3). “The pooled risk ratio obtained by the meta-analysis was
0.98” with a 95% confidence interval of 0.82-1.19. Id. at 114.
The Mouchet group concluded that their study and other studies “plead[] for
an incidental association between vaccination and demyelination rather than a
causal relationship.” They also went a step further to say: “These data do not
support the interesting hypothesis . . . regarding a biological plausibility based
upon a molecular mimicry of the vaccine with myelin basic protein.” Id. at 115.
The final study is by Klein and colleagues and was performed in 2012.
These researchers looked at people in the Kaiser Permanente system in California.
They found that the incidence of a hospital visit for a disease of the nervous system
did not meaningfully increase after a dose of the HPV vaccine. Klein at 1143
(table 2). However, the broad category of “diseases of the nervous system” is not
as specific as multiple sclerosis, which was studied in Scheller and Mouchet.
Two of Ms. Bravo’s experts criticized the Scheller study. Dr. Shoenfeld
preferred case reports to epidemiologic studies. Exhibit 311 at 1. However, case
reports contribute little, if anything, to evaluating claims of causation. See K.O. v.
Sec’y of Health & Human Servs., No. 13-472V, 2016 WL 7634491, at *11-12
(Fed. Cl. Spec. Mstr. July 7, 2016) (discussing appellate precedent on case
reports). For this reason, articles presenting case reports of multiple sclerosis are
not discussed here. See, e.g., Sutton (Exhibit 317).13
Dr. Lee took issue with the Scheller study and the Klein study. Exhibit 325
at 15, Exhibit 352 at 5-8. However, Dr. Lee’s curriculum vitae does not suggest
that he has expertise in epidemiology. See Exhibit 93.
Overall, these epidemiologic studies tend to undermine any claim that the
HPV vaccination either causes or aggravates multiple sclerosis. Special masters
have cited these studies in finding that the evidence did not preponderate in favor
of finding that the HPV vaccine can cause or worsen multiple sclerosis. See
Heddens v. Sec’y of Health & Hum. Servs., No. 15-734V, 2018 WL 5726991, at
13 Even further afield are case reports of demyelinating diseases other than multiple
sclerosis. As Dr. Sriram stated, “ADEM and NMO are two different diseases and are treated
differently from MS." Exhibit C at 12. Dr. Sriram’s view is corroborated by Mouchet and
others. In their meta-analysis, “Each neurological event (i.e., broad category of central
demyelination, ([multiple sclerosis, optic neuritis, Guillain-Barré syndrome]) was considered
separately, since the biological mechanisms leading to these events have little in common.”
Mouchet at 112.
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*3 (Fed. Cl. Spec. Mstr. Oct. 5, 2018) mot. for rev. denied, 143 Fed. Cl. 193
(2019); Maciel v. Sec’y of Health & Hum. Servs., No. 15-362V, 2018 WL
6259230, at *14, *27 (Fed. Cl. Spec. Mstr. Oct. 12, 2018).
However, epidemiology cannot prove a negative. Therefore, the three
methods about which Dr. Shoenfeld and Dr. Steinman have opined are addressed.
b) Persistence of Alum and Neurotoxicity
As previously stated, special masters have consistently not credited a theory
that adjuvants, such as alum, induce an autoimmune disease. Differentiating Dr.
Shoenfeld’s current theory from the theory he has expressed in other cases seems
difficult. While Ms. Bravo asserts that “Dr. Shoenfeld . . . did not assert ASIA,”
(Pet’r’s Supp’l Br. at 3), Dr. Shoenfeld presents a theory based upon alum. See
Exhibit 9 at 10-11.
Regardless of whether Ms. Bravo has actually disclaimed this theory, the
Secretary’s experts easily refuted it. For example, Dr. Romberg relied upon a large
study investigating how people exposed to aluminum respond. Exhibit A at 15,
Exhibit F at 6.
In this study, Allan Linneberg and colleagues investigated whether Danish
people who received subcutaneous allergen-specific immunotherapy developed
autoimmune diseases at an increased rate compared with Danish people who
received a different type of allergy treatment. Linneberg, Exhibit A-25. The
subcutaneous allergen-specific immunotherapy “contains aluminum hydroxide as
an adjuvant for depot vaccination.” Id. at 418. One disease specifically
investigated was multiple sclerosis. Id. at 415 (Table 1). The people who received
this therapy were at a slightly lower risk for developing an autoimmune disease.
The hazard ratio was 0.86 with a 95% confidence interval of 0.74-0.99. Id. at 413.
Thus, the Linneberg article tends to undermine the theory that exposure to
aluminum is likely to cause multiple sclerosis.
The next significant flaw in the theory that aluminum from the HPV vaccine
can cause neurotoxicity concerns the amount of aluminum in a vaccine. Dr.
Romberg presented information about the amount of aluminum contained in an
HPV vaccine and the hemodialysis of aluminum. Exhibit A at 15. Essentially, an
HPV vaccine includes an amount of aluminum much smaller than the amounts
given to mice in experiments that potentially show the harmful effect of aluminum.
Id. at 15-16. As Dr. Romberg states: “Even seemingly innocuous substances like
water or milk can be toxic if ingested in large amounts.” Special masters have
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reached the same conclusion. See Spahn v. Sec’y of Health & Hum. Servs., No.
09-386V, 2014 WL 12721080, at *17 (Fed. Cl. Spec. Mstr. Sep. 11, 2014), mot.
for rev. denied, 133 Fed. Cl. 588, 603 (2017); Snyder v. Sec’y of Health & Hum.
Servs., No. 01-162V, 2009 WL 332044, at *65 (Fed. Cl. Spec. Mstr. Feb. 12,
2009), mot. for rev. denied, 88 Fed. Cl. 706 (2009). The undersigned agrees with
the reasoning in these cases.
Finally, no persuasive evidence shows that aluminum in vaccines causes
multiple sclerosis. See Exhibit C (Dr. Sriram’s report) at 13.
In light of the above, Ms. Bravo has not met her burden of establishing that
the persistence of aluminum can lead to multiple sclerosis.
c) Alum Leading to IL-1beta
The next potential theory comes from Dr. Steinman, who asserted that the
alum component of the vaccine induces the production of a cytokine (IL-1beta)
and this cytokine contributes to the propagation of multiple sclerosis. See, e.g.,
Exhibit 133. Preliminarily, it must be pointed out (again) that whether Ms. Bravo
continues to put forward this theory is doubtful. None of her four briefs submitted
in advance of potential adjudication contain the term “cytokine” or “IL-1beta.”
Thus, Ms. Bravo could be found to have waived this theory. See Vaccine Rule
8(f).
Because Dr. Steinman’s theory based on alum involves aluminum, the
Linneberg article is an obstacle. As just explained, people who were exposed to
aluminum in that study did not develop any autoimmune disease (including
multiple sclerosis) at an increased rate. Likewise, Dr. Steinman appears not to
have accounted for the dose of alum and the body’s process for responding to it.
Special masters have generally, but not always, found theories based upon
cytokines causing harm unpersuasive. See, e.g., O.M.V. v. Sec’y of Health &
Hum. Servs., No. 16-1505V, 2021 WL 3183719, at *43-46 (Fed. Cl. Spec. Mstr.
June 6, 2021) (flu vaccine not shown to cause multiple sclerosis or acute
disseminated encephalomyelitis), mot. for rev. denied, 2021 WL 6124731 (Fed. Cl.
2021); Rupert v. Sec’y of Health & Hum. Servs., No. 15-841V, 2021 WL
1832909, at *36-39 (Fed. Cl. Spec. Mstr. May 1, 2021) (flu vaccine was not shown
to aggravate glomerulonephritis); McKown v. Sec’y of Health & Hum. Servs., No.
15-1451V, 2019 WL 4072113, at *50 (Fed. Cl. Spec. Mstr. July 15, 2019) (finding
that an HPV vaccine was not shown to cause postural tachycardia syndrome,
stating that the “fact that cytokine upregulation is promoted by vaccination – a
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medically reliable assertion standing alone – does not mean that this cytokine
increase is definitionally harmful,” and rejecting ASIA theory); But see Switzer v.
Sec’y of Health & Hum. Servs., No. 18-1418V, 2022 WL 4482721, at *17 (Fed.
Cl. Spec. Mstr. Aug. 29, 2022) (flu vaccine and pneumococcal conjugate vaccines
shown to cause systemic inflammatory response syndrome).
In other cases, special masters have rejected the theories based upon alum.
Samuels v. Sec’y of Health & Hum. Servs., No. 17-071V, 2020 WL 2954953, at
*20 (Fed. Cl. Spec. Mstr. May 1, 2020) (not crediting Dr. Steinman’s opinion that
the Tdap vaccine can cause multiple sclerosis or acute disseminated
encephalomyelitis and indicating that Dr. Steinman’s alum theory was close to the
discredited ASIA theory); Zumwalt v. Sec’y of Health & Hum. Servs., No. 16-
994V, 2019 WL 1953739, at *18 (Fed. Cl. Spec. Mstr. Mar. 21, 2019) (not
crediting Dr. Steinman’s theory that alum adjuvant in DTaP played a role in
causing petitioner’s seizures), mot. for rev. denied, 146 Fed. Cl. 525, 539-40
(2019). The undersigned agrees with the reasoning in these decisions, and Ms.
Bravo has not presented any persuasive evidence that theories based upon alum are
reliable.
Under the circumstances in which Ms. Bravo has not meaningfully advanced
this theory, evidence contrary to the theory is in the record, and the caselaw trends
against the theory, a more elaborate discussion is not required. Ms. Bravo has not
established the persuasiveness of the theory that alum worsens (or causes) multiple
sclerosis.
d) Molecular Mimicry
A more detailed discussion, however, is appropriate for the last theory. Ms.
Bravo has indisputably advanced molecular mimicry to explain how an HPV
vaccination can aggravate multiple sclerosis.
Because special masters are often called upon to evaluate the persuasiveness
of the theory of molecular mimicry, the Court of Federal Claims and the Court of
Appeals for the Federal Circuit have considered molecular mimicry in their
appellate role. In December 2019, the undersigned identified the leading
precedents as W.C. v. Sec’y of Health & Hum. Servs., 704 F.3d 1352 (Fed. Cir.
2013), and Caves v. Sec’y of Dep’t. of Health & Hum. Servs., 100 Fed. Cl. 119
(2011), aff’d sub nom., 463 F. App’x 932 (Fed. Cir. 2012). Tullio v. Sec’y of
Health & Hum. Servs., No. 15-51V, 2019 WL 7580149, at *12-14 (Fed. Cl. Spec.
Mstr. Dec. 19, 2019), mot. for rev. denied, 149 Fed. Cl. 448 (2020). While Tullio
describes those cases in more detail, their essence appears to be that although
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molecular mimicry is accepted in some contexts, special masters may properly
require some empirical evidence to show that a particular vaccine can cause a
particular disease.
In the next approximately three years, appellate authorities reviewing
decisions involving molecular mimicry have generally endorsed the approach of
looking for some evidence that persuasively shows that a portion of a vaccine
resembles a portion of human tissue, which contributes to causing the disease, and
that the immune system will respond to the relevant amino acid sequence.14
Chronologically, the list of more recent appellate cases begins with the opinion in
Tullio, which denied the motion for review. 149 Fed. Cl. 448, 467-68 (2020).
Another example in which the Court of Federal Claims held that the special
master did not elevate the petitioner’s burden of proof in the context of evaluating
the theory of molecular mimicry is Morgan v. Sec’y of Health & Hum. Servs., 148
Fed. Cl. 454, 476-77 (2020), aff’d in non-precedential opinion, 850 F. App’x 775
(Fed. Cir. 2021). In Morgan, the Chief Special Master found that petitioner had
not presented persuasive evidence about a relevant antibody. Id. at 477. The Chief
Special Master also noted that the articles about the relevant disease do not list the
wild flu virus as potentially causing the disease. Id. When examining this
analysis, the Court of Federal Claims concluded: “the Chief Special Master did not
raise the burden of causation in this case; petitioner simply failed to meet it.” Id.
The Federal Circuit also evaluated the Chief Special Master’s approach in
Morgan. The Federal Circuit concluded: “We discern no error in the special
master’s causation analysis.” 850 F. App’x 775, 784 (Fed. Cir. 2021).
Most other recent appellate cases follow this path. See, e.g., Duncan v.
Sec’y of Health & Hum. Servs., 153 Fed. Cl. 642, 661 (2021) (finding the special
master did not err in rejecting a bare assertion of molecular mimicry); Caredio v.
Sec’y of Health & Hum. Servs., No. 17-79V, 2021 WL 6058835, at *11 (Fed. Cl.
Dec. 3, 2021) (indicating that a special master did not err in requiring more than
homology and citing Tullio); Yalacki v. Sec’y of Health & Hum. Servs., 146 Fed.
Cl. 80, 91-92 (2019) (ruling that special master did not err in looking for reliable
evidence to support molecular mimicry as a theory); but see Patton v. Sec’y of
Health & Hum. Servs., 157 Fed. Cl. 159, 169 (2021) (finding that a special master
14 The term “homology” is used when discussing molecular mimicry. “Homology” is
defined as “the quality of being homologous; the morphological identity of corresponding parts;
structural similarity due to descent from a common form.” Dorland’s at 868.
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erred in requiring petitioner submit a study to establish medical theory causally
connecting flu vaccine to brachial neuritis).
Here, both Dr. Steinman and Dr. Shoenfeld contribute to Ms. Bravo’s claim.
The Secretary’s experts, Dr. Romberg and Dr. Sriram, oppose this theory. Their
opinions regarding molecular mimicry are summarized.
(1) Petitioner’s Experts
Dr. Steinman’s theory contains several steps. First, Dr. Steinman accesses a
resource the National Institute of Health makes available to the public that
provides the series of amino acids for numerous proteins, the basic local alignment
search tool (“BLAST”). Dr. Steinman enters a protein found in the HPV vaccine,
the major capsid L1. Exhibit 70 at 9. Dr. Steinman then enters a protein (myelin
basic protein) that, according to Dr. Steinman, is attacked to cause multiple
sclerosis. The BLAST program determines the degree to which the sequence of
proteins overlap. Dr. Steinman then enters a second protein also potentially
involved in the development of multiple sclerosis (myelin oligodendrocyte-
glycoprotein) and the BLAST program presents another set of results. (Note: Dr.
Sriram disagrees with the assertion that attacks on myelin basic protein and myelin
oligodendrocyte-glycoprotein cause multiple sclerosis.) Dr. Steinman next
searches the output of sequence similarity to identify places in which five of eleven
amino acids are identical. Id. at 10. From this process, Dr. Steinman concluded
that the amount of homology between a portion of the HPV vaccine and either
myelin basic protein or myelin oligodendrocyte-glycoprotein would allow a
person’s immune system to misfire. Instead of attacking the vaccine, the immune
system attacks host tissue, myelin basic protein or myelin oligodendrocyte-
glycoprotein. Id. at 17.
Later, in his fourth report, Dr. Steinman added another step. He consulted a
second resource from the National Institute Health, the immune epitope database.
Exhibit 349 at 2. The resource shows that the amino acid sequences Dr. Steinman
identified in his BLAST searches are found in people. Id. at 8. To Dr. Steinman,
this additional step “increased the stringency.” Id. at 2.
While Dr. Shoenfeld generally deferred to Dr. Steinman on the topic of
molecular mimicry, Dr. Shoenfeld added some different opinions. Dr. Shoenfeld
maintained that the adjuvant in the HPV vaccine could enhance an immune-
mediated cross-reaction. Exhibit 9 at 11-12.
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(2) Respondent’s Experts
Both Dr. Romberg and Dr. Sriram disputed the persuasiveness of the theory
that an HPV vaccination can worsen multiple sclerosis via molecular mimicry. Dr.
Romberg’s basic point was that the BLAST searches have produced results with
such “a low degree of similarity that [they] cannot be reliably differentiated from a
random pairing.” Exhibit A at 13. Dr. Romberg’s critique rests upon two points.
The first is a statistical measurement called an “E value,” which is discussed more
below. The second is that Dr. Romberg also searched the BLAST program and
discovered many proteins in common pathogens that exceeded the degree of
homology Dr. Steinman found. Id. at 14.
Dr. Romberg later turned to Dr. Steinman’s use of the immune epitope
database. Dr. Romberg found Dr. Steinman’s results “objectionable” for two
reasons. Exhibit H at 4. First, Dr. Steinman “leniently permits epitopes with only
70% homology to his search sequence (the lowest % allowed by the search
engine).” Id. Second, Dr. Steinman’s technique “filters out all non-immunogenic
epitopes which introduces a significant and highly problematic confirmation bias.
His searches are designed to hide evidence that an epitope is NOT immunogenic.”
Id. Dr. Romberg concludes that “this dangerous combination of analytic leniency
and susceptibility to confirmation bias does not offer ‘filtration’ as Dr. Steinman
claims but rather contaminates his data with non-random errors that are amplified
(not filtered out) as it moves from one analysis tier to the next.” Id.
As a neurologist, Dr. Sriram brought a different perspective on Dr.
Steinman’s molecular mimicry. Dr. Sriram contended that the pathology of
multiple sclerosis has not been shown to involve either of the proteins that Dr.
Steinman used in his BLAST searches, myelin basic protein and myelin
oligodendrocyte-glycoprotein. Exhibit C at 12-13.
(3) Analysis
Introductory Points. A few matters warrant mentioning at the beginning of
the analysis. First, Ms. Bravo has advanced this theory in her briefs. E.g. Pet’r’s
Supp’l Br. at 4. However, Ms. Bravo’s arguments are not well developed. For
example, after the Secretary challenged many details of the molecular mimicry
theory (Resp’t’s Br. at 24-27), Ms. Bravo’s ensuing brief simply repeated much of
her prior brief and did not refute the objections the Secretary had interposed. See
Pet’r’s Reply at 4-5.
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Second, special masters have evaluated the theory of molecular mimicry
differently. These disparate outcomes may reflect differences among finders of
fact. Lampe v. Sec'y of Health & Human Servs., 219 F.3d 1357, 1368 (Fed. Cir.
2000).
Assessment. Ms. Bravo has not met her burden of establishing that
molecular mimicry is a persuasive theory to explain how an HPV vaccination can
worsen multiple sclerosis. As discussed above, appellate precedents have tended
to require petitioners to demonstrate the reliability of the molecular mimicry
theory. Considered as a whole, the evidence does not support a finding that Ms.
Bravo has crossed that threshold. Specific problems include: (1) the inconsistency
with epidemiology, (2) the commonness of short stretches of similarity in amino
acids, (3) the failure of Ms. Bravo and Dr. Steinman to establish with preponderant
evidence that any similarity is biologically relevant, and (4) the failure of Ms.
Bravo and Dr. Steinman to establish with preponderant evidence that any attack on
the substance containing the amino acids Dr. Steinman has identified will worsen
(or cause) multiple sclerosis.
First, as noted above, large epidemiologic studies, involving hundreds of
thousands of people, have not detected an increased incidence of multiple sclerosis
among people who received an HPV vaccine. The consistency in the failure to
detect any heightened risk led one group of researchers to comment that the “data
do not support the interesting hypothesis . . . regarding a biological plausibility
based upon a molecular mimicry of the vaccine with myelin basic protein.”
Mouchet at 114.
Second, overlapping sequences in amino acids are relatively common.
Although Dr. Romberg made this point, see Exhibit A at 13, articles that Dr.
Shoenfeld cites determined how common homology is. Using one part of the HPV
vaccine, a researcher discovered more than eighty sequences in which seven amino
acids line up with amino acid sequences in the human genome exactly. Kanduc
(Exhibit 321 at 65. Thus, Dr. Steinman’s identification of some parts of the HPV
vaccine containing some sequences of amino acids that resemble (five out of
eleven) some portions of the nervous system is not particularly surprising.
Third, and relatedly, Dr. Steinman has not established that the homologies
he identified have any biologic significance. A paper that Dr. Steinman cited in his
report (Exhibit 70 at 13) investigated this point. This group of researchers found
that bioinformatic “searches for short amino acid sequence matches of eight amino
acids or fewer to identify proteins as potential crossreactive allergens is a product
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of chance and adds little value to allergy assessments for newly expressed
proteins.” Silvanovich (Exhibit 84).
Fourth, Dr. Steinman has not established that either myelin basic protein
(MBP) or myelin oligodendrocyte-glycoprotein (MOG) is the specific tissue
attacked in multiple sclerosis. Dr. Sriram questioned whether “reactivity to either
MBP or MOG is sufficient to trigger an autoimmune response.” Exhibit C at 13.
He added: “In the 50 or [sic] years since autoimmunity to myelin antigens have
been suggested as a cause of MS, they have not been proven. Many therapies
targeting autoimmune response to MBP antigen have failed.” Id. at 12. Although
Dr. Steinman responded to Dr. Sriram’s report, Dr. Steinman did not address this
specific point. See Exhibit 304. Thus, crediting Dr. Steinman’s focus on myelin
basic protein or myelin oligodendrocyte-glycoprotein is difficult. See Taylor v.
Sec’y of Health & Hum. Servs., No. 13-700V, 2018 WL 2050857, at *23 (Fed. Cl.
Spec. Mstr. Mar. 9, 2018) (questioning whether Dr. Steinman had presented
reliable evidence for the likely target of an attack resulting in acute disseminated
encephalomyelitis or multiple sclerosis).
Overall, the gaps and unexplored assumptions in Dr. Steinman’s theory that
molecular mimicry can worsen (or cause) multiple sclerosis are too much for Ms.
Bravo to overcome. She has not presented sufficient evidence to make this theory
persuasive. Thus, she has not presented preponderant evidence.
The finding in Ms. Bravo’s case is based upon the evidence in her case,
although the outcome is consistent with the results in other cases. Maciel v. Sec’y
of Health & Hum. Servs., No. 15-362V, 2018 WL 6259230, at *27-28 (Fed. Cl.
Spec. Mstr. Oct. 12, 2018); L.Z v. Sec’y of Health & Hum. Servs., No. 14-920V,
2018 WL 5784525, at *17-20 (Fed. Cl. Spec. Mstr. Aug. 24, 2018).
2. Loving Prong 5 / Althen Prong 2
Even if Ms. Bravo had established the persuasiveness and reliability of any
theory that the HPV vaccine can worsen (or cause) multiple sclerosis generally, she
would still be required to establish with preponderant evidence that the vaccination
harmed her specifically. Her proof on this point is also lacking.
As explained in the previous section, among the people whom Ms. Bravo
retained, Dr. Steinman is the only one who came close to presenting a persuasive
theory of how the HPV vaccine might have injured Ms. Bravo. Thus, his reports
are the focus of the next prong as well.
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In Dr. Steinman’s first report, his section regarding the “Logical Sequence of
Cause and Effect” consists of four sentences. Exhibit 70 at 22. These sentences
summarize the two potentially causal theories Dr. Steinman put forward. None of
these sentences discuss Ms. Bravo at all. Dr. Steinman has not identified any facts
in Ms. Bravo’s history that support finding the HPV vaccine had any harmful
effects.15
Dr. Steinman’s remaining reports do not meaningfully fill this gap. See
Exhibits 133, 304, 359 (addressing MRIs), 400 (addressing opinions of
neuroradiologists), 415 (presenting studies on Epstein-Barr virus and multiple
sclerosis), 427 (responding to Dr. Romberg’s opinion on the Epstein-Barr virus
studies).
At best, in the report in which Dr. Steinman explicitly addressed the Loving
prongs, his section on “logical sequence” is one sentence. Dr. Steinman states:
“The vaccine with significant mimicry with MOG and myelin basic protein
triggered an immune response that has been linked to optic neuritis and MS."
Exhibit 349 at 13. That is the total of Dr. Steinman’s writing on the topic in this
report. This content is too conclusory to be persuasive. See Song v. Sec'y of Dep't
of Health & Hum. Servs., 31 Fed. Cl. 61, 67–68, (affirming Special Master’s
decision to give little weight to a doctor’s conclusion that the vaccine caused the
alleged injuries where the doctor only made conclusory statements without
explanation), aff'd, 41 F.3d 1520 (Fed. Cir. 1994); see also Kreizenbeck v. Sec'y of
Health & Hum. Servs., No. 08-209V, 2018 WL 3679843, at *32 n.44 (Fed. Cl.
June 22, 2018) (“when a petitioner seeks to advance causation theories based on
conclusory arguments that . . . reflect conclusory expert statements that are not
themselves backed up with reliable scientific support, the absence of such evidence
. . . can be noted in evaluating if the petitioner has carried his burden of proof.”),
mot. for rev. denied, 141 Fed. Cl. 138 (2018), aff’d, 945 F.3d 1362 (Fed. Cir.
2020).
Ms. Bravo’s argument matches the thinness of this evidence. She concludes
that the HPV vaccine, “when administered to [Ms. Bravo] must have acted upon
the [existing] Multiple Sclerosis causing further damage to the area of the brain,
resulting in the aggravation of the disease process with the development of serious
and disabling clinical signs and symptoms that occurred.” Pet’r’s Br. at 21.
15 The sequence of events might be supportive. They are discussed in the following
section on timing.
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However, Ms. Bravo fails to identify any evidence (other than the sequence of
events) to show that a vaccine-induced injury “must have” happened.
The parties were directed to identify any treating doctors who associated Ms.
Bravo’s neurologic problem with the HPV vaccination. Order, issued March 26,
2021, at 9. Ms. Bravo did not point to any treating doctors helpful to her case. See
Pet’r’s Br. at 20-21.
In contrast, the Secretary and Dr. Sriram point out that Dr. Langer-Gould
treated Ms. Bravo. Resp’t’s Br. at 29 n.33, citing Exhibit C at 16; see also Exhibit
3 at 446 (identifying Dr. Langer-Gould as a specialist in multiple sclerosis). This
relationship is significant to the Secretary because (a) Dr. Langer-Gould has
written articles investigating whether vaccines cause multiple sclerosis and (b) did
not connect Ms. Bravo’s HPV to her multiple sclerosis.
The Secretary could have done more to prove these arguments. The
Secretary did not submit any papers by Dr. Langer-Gould, although special masters
have discussed such papers. See Harrington v. Sec’y of Health & Hum. Servs.,
No. 14-43V, 2018 WL 4401976, at *21-22, 24 (Fed. Cl. Spec. Mstr. Aug. 14,
2018).
More significantly, the Secretary has not cited evidence that Dr. Langer-
Gould actually knew that Ms. Bravo received the HPV vaccination. See Resp’t’s
Br. at 29. Dr. Langer-Gould’s history from her first appointment with Ms. Bravo
does not memorialize Ms. Bravo’s vaccination. See Exhibit 3 at 404-07. While
Dr. Langer-Gould might have constructive knowledge of the vaccination in that it
is discussed in the Kaiser medical records, which exceed 1500 pages, ascribing this
knowledge to Dr. Langer-Gould seems unjustified.
Ultimately, the Secretary does not bear the burden in this off-Table case to
present evidence that treating doctors rejected the claim that the HPV vaccine
harmed Ms. Bravo. It is Ms. Bravo’s burden to show a “logical sequence of cause
and effect” that the HPV vaccine harmed her. The absence of any affirmative
statements from treating doctors is one reason she has not met this burden.
Quintana v. Sec'y of Health & Hum. Servs., No. 15-1273V, 2022 WL 1873849, at
*12, 14 (Fed. Cl. May 18, 2022) (holding that the special master did not convert
missing evidence into evidence when she “not[ed] the absence of evidence,” as this
“is not the same as requiring evidence.”).
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3. Loving Prong 6 / Althen Prong 3
The next element concerns the timing. At several points, Ms. Bravo
emphasizes that her eye problem (optic neuritis) manifested approximately five
weeks after her final HPV vaccination. E.g. Pet’r’s Br. at 6, 11, 21-22; Pet’r’s
Supp’l Br. at 2. Her experts also discuss this sequence of events. Exhibit 70 (Dr.
Steinman’s report in the context of causation-in-fact) at 21; Exhibit 349 (Dr.
Steinman’s report in the context of significant aggravation) at 13.
Regardless of whether the optic neuritis is treated as the first manifestation
of multiple sclerosis for a causation-in-fact case or is treated as a manifestation of
an ongoing course of multiple sclerosis for a significant aggravation case, the
analysis is the same. Ms. Bravo appears to have credible evidence on this topic.
However, proof of a sequence of events in which a vaccination preceded a decline
in health does not mean the vaccine caused the problem. Grant v. Sec’y of Health
& Human Servs., 956 F.2d 1144, 1148 (Fed. Cir. 1992) (“Temporal association is
not sufficient, however, to establish causation in fact.”); L.Z v. Sec’y of Health &
Hum. Servs., No. 14-920V, 2018 WL 5784525, at *20 (“I cannot conclude from
this record that the flu vaccine had anything more than a temporal relationship to
Petitioner’s MS flare—and such a relationship is well understood in the Program to
have little evidentiary bearing when determining entitlement.”) (Fed. Cl. Spec.
Mstr. Aug. 24, 2018). Thus, her showing on this prong does not overcome her lack
of evidence on the other two elements discussed above.
V. A Hearing Is Not Necessary
Special masters possess discretion to decide whether an evidentiary hearing
will be held. 42 U.S.C. § 300aa-12(d)(3)(B)(v) (promulgated as Vaccine Rule 8(c)
& (d)), which was cited by the Federal Circuit in Kreizenbeck v. Sec’y of Health &
Hum. Servs., 945 F.3d 1362, 1365 (Fed. Cir. 2018). “A special master is not
obliged to hold an evidentiary hearing.” Oliver v. Sec’y of Health & Hum. Servs.,
133 Fed. Cl. 341, 354 (2017), aff’d, 900 F.3d 1357, 1363 (Fed. Cir. 2018).
Here, Ms. Bravo has had a fair opportunity to present her case. She
presented more than twenty reports from people whom she retained. She argued
her position in four briefs regarding her entitlement to compensation. She has not
demonstrated how oral testimony would affect the outcome of any of the issues.
Accordingly, the undersigned declines to convene a hearing.
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VI. Additional Comments
Ms. Bravo and her parents have struggled after the diagnosis of multiple
sclerosis. Exhibit 3 at 631-32. The challenges in living with a chronic disease are
certainly understandable. They deserve sympathy for their troubles and admiration
for how they have tried to address the hardships that have fallen on them.
It is also understandable that Ms. Bravo and her parents might point to the
third dose of the HPV vaccination as contributing to her health problems. After
all, before the vaccination, no one knew Ms. Bravo had at least one lesion in her
brain and no doctor had diagnosed her with multiple sclerosis. Then, from their
perspective, Ms. Bravo’s health turned upside down after the vaccination. It is
easy to blame the vaccination, and the Vaccine Program is the forum that primarily
resolves claims that a vaccine injured someone.
Ms. Bravo presented multiple experts and multiple theories in this litigation.
The multiplicity has not been advantageous. See Baron v. Sec’y of Health &
Human Servs., No. 14-341V, 2019 WL 2273484, at *17 (Fed. Cl. Spec. Mstr. Mar.
18, 2019) (petitioners “need to propose something more than taking a vague
‘kitchen sink’ approach and listing eleven mechanisms that have been previously
submitted in the Program for claims of vaccine-caused injury with various degrees
of success. Petitioners have listed many possibilities but have not identified a
sound and reliable explanation that can be applied to the vaccines and injury in this
case”). As discussed at length above, it appears that Ms. Bravo has disclaimed any
reliance upon Dr. Shaw and Dr. Lee by not advancing their opinions with any force
in her briefs. Nevertheless, as the Vaccine Act requires, the undersigned has
considered this evidence as part of the case.
The undersigned has also evaluated the parts of Ms. Bravo’s evidence that
are relatively stronger, the reports from Dr. Shoenfeld and Dr. Steinman. While
the reports from Dr. Shoenfeld and Dr. Steinman are better than the reports from
Dr. Shaw and Dr. Lee, the reports from Dr. Shoenfeld and Dr. Steinman remain
unpersuasive for many reasons listed above. Without a persuasive presentation,
Ms. Bravo is not entitled to compensation.
VII. Conclusion
Ms. Bravo’s case began with an allegation that an HPV vaccination caused
her to suffer multiple sclerosis. After the evidence showed, more likely than not,
that she had multiple sclerosis before the vaccination, the case transitioned to a
claim that the HPV vaccination significantly aggravated the multiple sclerosis.
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Regardless of the characterization, the evidence does not preponderate in favor of
finding that the HPV vaccination harmed Ms. Bravo. Ms. Bravo has not
established with preponderant evidence that the HPV vaccination can worsen (or
cause) multiple sclerosis. She also has not established that the HPV vaccination
harmed her. Accordingly, Ms. Bravo is not entitled to compensation.
The Clerk’s Office is instructed to enter judgment in accordance with this
decision unless a motion for review is filed. Information about filing a motion for
review, including the deadline, can be found in the Vaccine Rules, available
through the Court’s website.
IT IS SO ORDERED.
s/Christian J. Moran
Christian J. Moran
Special Master
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Appendix: List of Medical Articles Cited1
1. R. Inbar et al., Behavioral abnormalities in female mice following administration of
aluminum adjuvants and the human papillomavirus (HPV) vaccine Gardasil. 65
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1 All articles have been considered.

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