Bivalent COVID vaccines: When will studies begin in order to stay ahead of the multiple known (and unknown) variants?

The New York Times reported Monday (Jan. 25) that: “As a precaution, Moderna has begun developing a new form of its vaccine that could be used as a booster shot against the variant in South Africa . . . Moderna said it also planned to begin testing whether giving patients a third shot of its original vaccine as a booster could help fend off newly emerging forms of the virus.”

Also, BioNTech is “talking to regulators around the world about what types of clinical trials and safety reviews would be required to authorize a new version of the Pfizer-BioNTech vaccine that would be better able to head off the variant in South Africa."

This decision seems prudent especially given the following three unknowns:

• No “correlate of protection,” in terms of antibody levels that confer protection against SARS-CoV-2 infection, has been established for COVID-19 vaccines;
• No data on T-cell responses has been published on the effect of current vaccines against the variant “501Y.V.2 (B.351)” first reported from South Africa;
• How often this variant occurred in persons in South Africa who received any of the current first-generation COVID-19 vaccines. Sequencing of all “breakthrough” viruses that occur in COVID vaccine studies, to determine how often variants occur in vaccinees compared with placebo recipients, would provide valuable data on % vaccine efficacy whether in S. Africa, the USA, UK, Brazil (with its variant “P.1”) or elsewhere.

Looking ahead, it would also seem prudent to begin developing bivalent vaccines and testing e.g., with the current “first-generation” vaccines based on the original virus sequence from Wuhan (~January 7, 2020) plus the South African variant 501Y.V2.

Or depending on what is found with the Brazilian P.1 variant with regard to how similar it is to 501Y.V2 in terms of antibody neutralization after vaccination, and by convalescent sera from survivors of the first wave of infection before these variants emerged in Brazil and South Africa.

Having worked at the U.S. Food and Drug Administration vaccines division, I would not be surprised if FDA regulatory issues for the safety, immunogenicity, and efficacy of the first bivalent (or multivalent) COVID-19 vaccine would extend beyond those for a monovalent COVID-19 vaccine such as those already granted emergency use authorization or the proposed Moderna booster using the 501Y.V2 variant (monovalent vaccine).

All the more reason to start down the longer road to the first bivalent COVID vaccine today.