On March 6-7, 2024, I joined a group of other Lyme and tick-borne disease advocates meeting with members of the CDC and a representative from Pfizer in Atlanta.

Our goal was to develop a list of questions to help inform the Lyme vaccine program development and implementation if the Pfizer VLA15 Lyme vaccine (currently in phase 3 clinical trials) is approved for use in the U.S.

The advocates were invited in an effort to develop relationships that expand the CDC’s understanding of the lived experience of Lyme disease (from patients, caregivers and leadership from patient-driven research organizations).

From the beginning, I’ve aimed to be as transparent as possible with the Lyme community. As I shared in detail here, it was an extremely valuable meeting where the group brought forth scores of questions for Pfizer.

It has taken some time for the final list of questions to be compiled and reviewed by each of the participants. Below are the finalized questions as submitted to Pfizer today.

Setting the stage

This comprehensive list sets the stage for future communications with the CDC regarding any Lyme disease vaccines that may become available.

A special thanks goes out to Dr. Sue Visser of the CDC for coordinating the meeting and following through with all the details.

Also grateful to Dr. Lyle Petersen, Dr. Grace Marx and Dr. Paul Mead, CDC officials who stayed with us from start to finish. They listened to our personal stories and answered many technical questions.

And of course a HUGE shout-out to the other advocates in attendance: Wendy Adams, Bonnie Crater, Bruce Fries, Holiday Goodreau, Olivia Goodreau and Patricia Smith. (Click links to find out more about them.)

I sincerely hope we can get these questions answered. I will keep you informed as I learn more information from the CDC or Pfizer.

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 summary. 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, etc.)?
• 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, etc.) in order to opti­mize ti­ming of efficacy?

Questions About Post-Licensure

• Are there future studies planned if VLA15 if licensed in the U.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, etc.)?
• 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? [VAERS  stands for Vaccine Adverse Event Reporting System]
• 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 Department of Defense (DoD)

Questions About Post-Licensure

• What is the vaccine recommendation process for DoD?

LymeSci is written by Lonnie Marcum, a physical therapist and mother of a daughter with Lyme. She served two terms on a subcommittee of the federal Tick-Borne Disease Working Group. Follow her on Twitter: @LonnieRhea  Email her at: lmarcum@lymefaces.com.