The Race to Develop an Omicron-Specific Booster Vaccine

Omicron maintains its status as the predominant COVID-19 variant, and new vaccine boosters are being designed accordingly.

Recently, Pfizer-BioNTech, Moderna, and Sanofi and GlaxoSmithKline have all released promising data for COVID-19 vaccines optimized to protect against Omicron.

The Pfizer-BioNTech and Moderna mRNA COVID-19 vaccines were recently approved under Emergency Use Authorization (EUA) for individuals as young as 6 months of age. Though these vaccines still offer significant protection against severe or fatal COVID-19 disease, Omicron is causing breakthrough infections at rates unprecedented by other variants.

Sanofi and GSK do not currently have an approved COVID-19 vaccine. However, they announced positive results from 2 trials for their COVID-19 booster candidate earlier this month. The booster is modeled on the Beta variant antigen, and features an adjuvant from GSK.

Sanofi reported data from 2 clinical trials, VAT02 Cohort 2 and COVIBOOST VAT013. In the former phase 3 study, the booster candidate significantly raised antibody titers above baseline against numerous variants of concern. Antibodies were boosted 15-fold against the D614 parent virus and 30-fold against the Beta variant in a cohort of adults with prior mRNA COVID-19 vaccinations.

Most notably, there was a 40-fold increase in antibody titers against the Omicron BA.1 variant. Compared to the booster vaccine based on the original parent COVID-19 virus, the Sanofi-GSK booster candidate elicited double the number of neutralizing antibodies against Omicron BA.1 and BA.2.

In the 13000-sibject study cohort, the booster demonstrated 72% efficacy against Omicron. In participants who previously had contracted and recovered from a COVID-19 infection, the efficacy against symptomatic Omicron infection rose to 93.2%.

Pfizer-BioNTech is developing monovalent and bivalent Omicron-adapted mRNA vaccines. Pfizer-BioNTech and Moderna had both yet to produce efficacy data for their Omicron booster candidates. However, today, Pfizer-BioNTech shared results suggesting their Omicron-adapted monovalent booster elicited neutralizing geometric titers 13.5 (at 30 µg) and 19.6-fold (at 60 µg) higher than their original COVID-19 vaccine. Their bivalent booster candidate exhibited 9.1 (at 30 µg) and 10.9-fold (at 60 µg) increased antibody responses against Omicron.

“The data show the ability of our monovalent and bivalent Omicron-adapted vaccine candidates to significantly improve variant-specific antibody neutralization responses,” said Ugur Sahin, MD, the CEO and cofounder of BioNTech. “Omicron has newly evolving sublineages that have outcompeted BA.1 and exhibit a trend of increasing potential for immune escape. We will therefore remain vigilant and are prepared to rapidly adapt our Omicron-adapted vaccine candidates to emerging sublineages if epidemiological and laboratory data suggest.”

Pfizer-BioNTech said laboratory studies of the booster candidates had safety and tolerability profiles comparable to that of the original Pfizer-BioNTech. The Omicron-specific boosters neutralized the BA.4 and BA.5 variants to a slightly lesser extent than they did BA.1.

Finally, Moderna announced new clinical data for its bivalent Omicron booster candidate, mRNA-1273.214. Among study participants who were previously vaccinated and boosted, a 50 µg booster dose of mRNA-1273.214 generated potent neutralizing antibody responses against Omicron subvariants BA.4 and BA.5 in all participants, regardless of prior infection status.

mRNA-1273.214 boosted antibody titers against BA.4/BA.5 5.4-fold above baseline in all participants, and 6.3-fold in seronegative participants. At 1 month after recieiving the booster candidate, neutralizing geometric mean titers against the BA.4 and BA.5 subvariants were 941 in all participants, and 727 in seronegative participants.

“In the face of SARS-CoV-2's continued evolution, we are very encouraged that mRNA-1273.214, our lead booster candidate for the fall, has shown high neutralizing titers against the BA.4 and BA.5 subvariants, which represent an emergent threat to global public health,” said Stéphane Bancel, the CEO of Moderna. “We will submit these data to regulators urgently and are preparing to supply our next generation bivalent booster starting in August, ahead of a potential rise in SARS-CoV-2 infections due to Omicron subvariants in the early fall.”