On March 7, 2024 a meeting was hosted by the CDC that consisted of a small group of expert-advocates to develop the CDC’s understanding of the lived experience of Lyme disease. The goal of this meeting was to compile a list of individual questions to understand more about a future Lyme disease vaccine, and the VLA15 vaccine in particular, given it was the only vaccine candidate being evaluated in phase 3 clinical trials as of the date of this meeting. Pat Smith reported on this meeting in the President’s Blog – In-depth Synopsis of Advocate Vaccine Meeting Hosted by CDC. The following is a list of all the questions contributed by the participants of the meeting. These questions were shared with a Pfizer representative by the CDC on March 8, 2024. As of April 30, 2024, there has been no response by Pfizer. 

Lyme Disease Vaccine Technical Consultation, March 7-8, 2024
Meeting Product

Background

On March 7, 2024 a small group of expert-advocates were convened to compile a list of individual
questions that they have about a future Lyme disease vaccine, and the VLA15 vaccine in particular, given
it was the only vaccine candidate being evaluated in phase 3 clinical trials as of the date of this meeting.
The following is a list of all the questions contributed by the participants. These questions were shared
with a Pfizer representative on March 8, 2024.

Questions for Pfizer

General Questions

• Why didn’t Pfizer engage the Lyme disease community sooner in the vaccine development process?
• Can you tell us why a presentation about VLA15 wasn’t provided by Pfizer for this meeting?
• Is there a way to have access to presentations previously given at scientific conferences (e.g., the Gordon Conference)?
• Would Pfizer be able to make a presentation about VLA15 and the results of the clinical trials at a meeting convened by CDC with a broad group of researchers and non-researchers from the Lyme community?

Questions About Vaccine Development

• Which OspA fragments were used in VLA15?
• Does the ST1-OspA that was used cover the strains in California?
• How was OspA modified to prevent autoimmune reactivity to HLA/LFA?
• What are the vaccine technology and ingredients? (Background note: there are concerns about the danger of those with alpha-gal receiving mammalian products via healthcare products.)
• Why was OspA chosen as the target, given the LYMERix® concerns?
• How is this vaccine similar and different than LYMERix®?
• Specifically, how have the vaccine’s developers edited out the putative mimic of hLFA-1? Is there any data to confirm that additional epitopes are not problematic, if the mimic of hLFA-1 is not the only one that caused an autoimmune reaction in LymeRix? What data convinced you that VLA15 would be safer than LYMERix®?
• Did Pfizer investigate any of the peer-reviewed articles on the problems that were thought to have affected those who took LYMERix® (for example, those related to HLA or demyelination)?
  • If so, please provide a If not, why?
• What happened to the Baxter Lyme disease vaccine?
  • Did Pfizer look into this vaccine?
  • Did Pfizer acquire any portion of the Baxter Lyme disease vaccine division?
• What happened to the Connaught ImmuLyme vaccine?
  • Did Pfizer look into this vaccine?

• How does VLA15 prevent Lyme disease?
• How long does it take for human antibodies to develop after the OspA vaccine?
  • How long does this response continue?
• How long does it take for the antibodies in the human blood to deactivate the Borrelia in the tick (minutes, hours, days)?
• What are the transmission assumptions used in the development of VLA15?
• Do you have plans for other tickborne disease vaccines (e.g., babesiosis, bartonella, relapsing fever species)?
• Do you keep a repository of trial samples for use in future research?
  • If so, who can access them?
• What are the greatest challenges Pfizer has faced in developing this vaccine?
  • What challenges do you anticipate facing in the future?
• Is there anything you can tell us that wasn’t in the press releases?

Questions About the VLA15 Trials

• On the April 2022 press release, can you please clarify whether the pediatric immunogenicity response was similar or different for 2 or 3 dose schedule?
• Who conducts Phase 4 studies?
  • Does Pfizer intend to conduct Phase 4 studies?
• One of the press releases references “observer blind”. Is “observer blind” different from “double blind”?
• Can you please clarify the calculus of going from 6,000 target participants to the final recruited total of 9,437 participants?
• Were data from the 3,000 discontinued VALOR participants retained?
  • If so, how will they be analyzed?
• Does the VLA15 series need to start at a specific time of year to optimize immunological response?
• On what data did Pfizer base the timing of a 12-month booster? If you will target boosters before “peak season” (as referenced in the 12/4/23 press release), how will “peak season” be defined?
• In the 2/4/22 press release, how was the “subset” of phase 2 participants selected for the booster study?
• How many of the 9,437 participants were enrolled from the US?
  • Europe?
  • Canada?
• How do we know that one booster is sufficient when the initial series required 3 vaccines?
• What were the participant incentives?
• Would you conduct subgroup analyses of those who contracted COVID-19 during the study?
• In the clinical trials, participants were either “Lyme naïve” or had “cleared past infection”. What diagnostic method was used to determine a person’s Lyme status?
  • Did you test for other infections?
  • What diagnostics were run overall, across time?
• What Lyme disease testing method is being used to verify vaccine efficacy?
• Do you have data on the safety and efficacy of this vaccine in people who are pregnant?
  • Do you have data on people who became pregnant during the trial? If so, what did the data show?
  • If there are resulting pregnancies, will those pregnancies be followed, and will any offspring born be followed over time especially for any Lyme cases (e.g., vaccine failures)? Will specimens be collected?
• Did you enroll people who were known to have non-Lyme tickborne diseases?
  • If so, can you do subgroup analyses of them?
• Have you evaluated the safety and efficacy of VLA15 in immunocompromised patients? If not, will you? How did you define “immunocompromised”?
• Did you enroll people with non-communicable diseases that weren’t part of the exclusion criteria?
  • Do you intend to do subgroup analyses of this population?
• What is the threshold to determine protection and how is this threshold determined?
  • How long does protection last?
• How long after getting the 3rd dose does it take to be fully protected?
• Are you partially protected after one or two doses?
  • If so, how much?
• How long are clinical trial participants being monitored?
  • If so, how?
• Are there any sex-based differences in the immunological response?
• Is there any therapeutic value to VLA15?
• Can you provide the GCP guidelines that were violated by Care Access, leading to the removal of this contractor?

Questions About Adverse Events and Side Effects

• Can you assess the safety and efficacy of VLA15 in those who have tickborne diseases?
  • Do you have plans to conduct subgroup analyses?
• What is the safety profile and what are the side effects of VLA15?
  • What were the worst side effects?
• Do you have any plans to evaluate the safety and efficacy of VLA15 in patients with persistent Lyme disease?
• Can you get VLA15 if you’re sick (e.g., have cold symptoms, )?
• Can this vaccine be co-administered with other vaccines?
  • If not, what is the wait time?
• Is there a plan to co-administer the Lyme vaccine with the fall vaccines (e.g., COVID, flu, ) in order to optimize timing of efficacy?

Questions About Post-Licensure

• Are there future studies planned if VLA15 if licensed in the S, post-licensure (e.g., with those excluded from VALOR: pregnant people, breastfeeding people, elderly people)?
• Are there plans to expand clinical trials to other regions of the world?
• Where is/will VLA15 be manufactured?
• What will the cost be?
  • Will it be covered by insurance?
  • If so, under what circumstances?
• If recommendations from ACIP are restrictive to geography, will Pfizer conduct additional studies or trials to establish use in other geographic areas to support broader uptake?
• What are the logistics around vaccine implementation (shelf life, storage requirements, )?
• Are there anticipated impacts of VLA15 on subsequent diagnostic testing for future infections (e.g., false positives for Lyme disease, etc.)?
• Will Pfizer enlist patient access programs to support uptake and accessibility to the vaccine?

Questions about Communications and Rollout

• When can the public have access to the marketing plan described in one of the VLA15 press releases?
• How will Pfizer ensure that the public understands the scope of protection from VLA15, and specifically that it will not protect the public from tickborne diseases other than Lyme disease?

Questions for CDC

General Questions

• Would Pfizer be able to convene a meeting at which the VLA clinical trial findings could be presented to the broad research and non-research Lyme community?

Questions About Adverse Events and Side Effects

• When a person reports to VAERS, is their report/symptom placed into a coding system (used by the FDA or others), or are their symptoms investigated and analyzed at face value?
• What is the reporting and investigation process of VAERS?
• Do we currently (during the phase 3 clinical trial) have public access to adverse event data from the clinical trials (through VAERS or otherwise)?
  • Does VAERS receive reports pre-licensure?
  • If so, how are VAERS reports considered by FDA for licensure?

Questions About Post-Licensure

• What can be shared publicly about the ACIP member vetting process?
  • What is the conflict of interest process for vetting ACIP members?
    • If a person is shown to have a conflict of interest, is there a process to remove them?
    • Is this information disclosed?
  • Will VLA15 be considered for the Vaccines for Children program?
  • Would special populations get recommendations in the future, even if they were not included in the clinical trials?
  • Do states have an independent role in determining if a vaccine is included in the Vaccines for Children program?

Questions about Communications and Rollout

• What are CDC’s plans for vaccine rollout, including website content?
• How will CDC incorporate information about vaccine safety monitoring systems in its vaccine rollout?

Questions for FDA

Questions About the VLA15 Trial

• Does FDA have a statement on why Pfizer discontinued a large number of participants in their US VALOR study?
• Why did FDA clear Care Access (contractor)?
  • Why were FDA’s findings different than Pfizer’s?
• If VAERS receives reports pre-licensure, how are these reports considered by FDA for licensure?

Questions for DoD

Questions About Post-Licensure

What is the vaccine recommendation process for DoD?

For More Information: 

Read Pat Smith’s President’s Blog on Advocate’s Vaccine Meeting

Read More LDA Articles on Pfizer Vaccine

Read Lyme Vaccine Meeting Article from Lymedisease.org

Read More from CDC on Lyme Vaccine