What should go into a booster shot for COVID-19?

With COVID-19 vaccines providing waning levels of protection against the evolving SARS-CoV-2 virus, the FDA convened its panel of independent experts to discuss the path forward for booster shots. “We have to give serious consideration to a booster campaign this fall to help protect us from another COVID-19 surge,” said the FDA’s Peter Marks at the start of the one-day VRBPAC meeting in late June. On the agenda: should boosters include the spike protein from the Omicron variant of the virus? If so, which sub-lineage of the variant is optimal? And, is a monovalent or bivalent booster best?

Three vaccine developers presented data. Pfizer and its partner BioNTech made the case for a monovalent mRNA booster that expresses the spike from the Omicron BA.1 variant, and for a bivalent mRNA candidate that expresses spikes from the ancestral form of the virus and from Omicron BA.1. Moderna showcased its bivalent mRNA vaccine candidate, also encoding the spikes of the ancestral and the Omicron BA.1 variant. Novavax’s NVX-CoV2373 is a recombinant protein subunit vaccine that is based on the spike of the original strain. As boosters, all of these candidates increased levels of neutralizing antibodies against the now-dominant Omicron BA.4 and BA.5 sub-lineages, compared to first-generation vaccines. Sponsors have yet to present clinical efficacy data from any of these.

Panellists debated whether to push vaccine developers to update their candidates to carry the BA.4/BA.5 spike protein — and highlighted the need for better insights into the correlation of vaccine efficacy with antibody levels and T cell activity. They voted 19 to 2 in favour of incorporating an Omicron spike into a booster vaccine, with varied opinions on sub-lineage prioritization.

“Bottom line, it seems like a BA.4/BA.5 bivalent was the sense of the committee,” summarized the FDA’s Peter Marks at the end of the meeting. The WHO favours a booster with an Omicron BA.1 composition, leading some panellists to call for a globally aligned booster development plan.

This is “science at its hardest,” said Marks. By the time irrefutable evidence is available for the best path forward, a new variant of the virus may have emerged.

Days before the meeting, Sanofi and GSK press released the first efficacy results from their bivalent recombinant protein subunit vaccine — using spike proteins from the ancestral and Beta variants. In a phase III trial in 13,000 adult volunteers, it had an efficacy of 65% against symptomatic COVID-19, and 75% efficacy in patients previously infected with COVID-19. The efficacy against Omicron-confirmed symptomatic disease was 72%.

Sanofi and GSK are hoping for a possible authorization later this year.