An FDA advisory committee is scheduled 4/6 to discuss what is the optimal strain composition for Covid-19 vaccines to address emerging variants. According to a just-posted briefing document, the panel will also discuss when and how frequently to consider strain composition changes, and what is the optimal timing for a Covid vaccine booster dose among the general population and among specific sub-populations.
FDA officials note that observational studies show that the primary Covid vaccinations have decreased effectiveness against the Omicron variants and waning effectiveness over time. They say that while the first booster doses restored waning vaccine effectiveness (VE), “observational studies have also indicated waning effectiveness of the first booster dose over time, mainly against mild disease, with some studies also suggesting waning effectiveness against hospitalization… The Israeli experience with second booster dose of the Pfizer-BioNTech Covid-19 vaccine in adults 60 years of age and older indicates that a second booster dose improves VE overall, including through a reduction in mortality, … although effectiveness against mild disease decreased during a 10-week follow-up period.”
The main issue, according to the briefing document, is that the current vaccines and boosters are based on the original Wuhan Covid strain. Current data suggest that vaccine composition may need to be modified in the future to provide the high level of efficacy demonstrated in the early vaccine clinical trials. FDA suggests that the process used to update annual seasonal influenza vaccines may be a good model for updating Covid vaccines/boosters.
To achieve a modified vaccine, FDA says that in addition to data to support manufacturing consistency, a modified vaccine would require clinical data (immunogenicity and safety studies) to support its use. Considerations for manufacturing, as well as nonclinical, and clinical data to support a modified vaccine are described in detail in the agency’s guidance “Emergency Use Authorization for Vaccines to Prevent COVID-19 (see Appendix 2: Evaluation of Vaccines to Address Emerging SARS-CoV-2 Variants).
Additionally, FDA notes that assumptions used to modify the influenza vaccines usually lead to a vaccine that is 60% effective in a good year. “When seasonal influenza vaccines are poorly matched with circulating strains of influenza virus, vaccine effectiveness is substantially reduced, particularly in more susceptible populations such as the elderly,” it says. “The most common reasons for a poorly matched influenza vaccine have relevance for Covid-19 vaccine composition recommendations.”
The agency says it is not uncommon for an antigenically distinct influenza virus to emerge after recommendations for the flu vaccine, or a flu virus may have been undetected at the time of vaccine composition recommendation. “The pattern of SARS-CoV-2 variant evolution and dominance is just as uncertain as that for influenza,” it says, adding that manufacturing issues that cannot be resolved in a timely manner can preclude production of a well-matched vaccine too.
