FDA posts advice on EUA for COVID-19 vaccines with Oct. 22 meeting materials: Monitoring for eosinophilic vaccine-induced enhanced respiratory disease

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By Daniel R. Lucey M.D., MPH, FIDSA

As promised by the U.S. Food and Drug Administration, the materials for the first public Vaccine Advisory Committee on Emergency Use Authorization (EUA) issues for COVID-19 vaccines Oct. 22 — Thursday — have been posted online as of today.

The agenda, Advisory Committee roster, and a one-page statement titled: “COVID-19 Vaccine Confidence Project” are also available.

The stated goal of this Vaccine Confidence Project, provided by the Reagan-Udall Foundation for the FDA, is “to provide the vaccine-hesitant with the information they need to make an informed decision regarding whether or not to receive a COVID-19 vaccine, when available.” Acknowledgement is made to “…barriers that lead so many Americans to feel hesitant about receiving a COVID-19 vaccine, when available, specifically perceptions related to FDA’s role in vaccine review and authorization/approval.”

The topics for the Thursday discussion (p. 2-3 of 38) include (my boldtype for emphasis) : “…what would be necessary for active safety follow up in  order to permit an ongoing assessment of the benefits and risks of a COVID-19 following issuance of an EUA,” as well as what studies “should be conducted, pre-and/or post-licensure, to evaluate the safety and efficacy of COVID-19 vaccine candidates, including in special populations (e.g., pediatric populations and pregnant women), and further evaluate the immunogenicity and duration of effectiveness of these vaccines”.

Notably, there is an updated four-page EUA guidance (p. 10-14 of the 38 total)  titled “APPENDIX II: Summary of Advice to Individual Sponsors to Questions Regarding Emergency Use Authorization of Vaccines to Prevent COVID-19” within the 38-page FDA Briefing Document for the Oct. 22 Vaccines and Related Biological Products Advisory Committee Meeting. Of the many key points in this recent EUA guidance, only two are cited below (my boldtype for emphasis and where “ERD” stands for “Enhanced Respiratory Disease”):

  • “Data from Phase 3 studies that includes a median follow-up duration of at least two months after completion of the full vaccination regimen to help provide adequate information to assess a vaccine’s benefit-risk profile…”.
  • “Sufficient cases of severe COVID-19 among study subjects to support low risk for vaccine-induced ERD (a total of 5 or more severe COVID-19 cases in the placebo group would generally be sufficient to assess whether the severe COVID-19 case split between vaccine vs. placebo groups supports a favorable benefit-risk profile or conversely raises a concern about ERD)”.

In my opinion, the legitimate concern over (some) vaccines against COVID-19 inducing “Enhanced Respiratory Disease (ERD)” is underappreciated. On page 6 of the 38-page FDA briefing document it is stated (my boldtype added) : “…a key safety concern for COVID-19 vaccines is the potential for vaccine-induced enhanced respiratory disease (ERD) when vaccine recipients are subsequently exposed to wild-type SARS-CoV-2. ERD associated with human coronavirus vaccines (SARS and MERS vaccines) has thus far been demonstrated only in animal models of SARS-CoV-1 and MERS-CoV and has been characterized by a Th2-biased immune response resulting in eosinophilic immune pathology.”

References cited for this Th2-biased vaccine-induced ERD are for SARS-CoV-1, and for MERS-CoV. In both studies increases in eosinophil (Th2) stimulating cytokines IL-5 and IL-13 were reported.

Of note, both these SARS and MERS vaccine studies in mice used inactivated vaccines. None of the current phase 3 studies in the USA are inactivated vaccines. Some inactivated vaccines against COVID-19, made by other nations, are in Phase 3 clinical trials on several continents. We should monitor those studies very closely, even though the United States has started withdrawing from the World Health Organization, and may not have immediate access to data from these vaccine studies overseas.

Dr. Daniel Lucey

Daniel Lucey, M.D. MPH, FIDSA, FACP, is an infectious diseases physician and adjunct professor of infectious diseases at Georgetown University Medical Center, a senior scholar at the Georgetown University O’Neil Institute, Anthropology Research Associate, Smithsonian Museum of Natural History and a member of the Infectious Diseases Society of America Global Health Committee.He has served as a volunteer medical responder to outbreaks that included the West Africa Ebola crisis. He has collected information on outbreaks starting in 2001 with cases of anthrax in 2001, and including smallpox vaccination 2002, SARS 2003, H5N1 Flu 2004, MERS in 2013, and Ebola in April, 2014, He has gathered, and  updated information on the spread of the coronavirus here since Jan. 6.

 

 

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