Moderna recently announced that in phase II/III clinical trials, its bivalent Omicron-targeting booster candidates (mRNA-1273.214 and mRNA-1273.222) generated a superior antibody response compared with a booster dose of mRNA-1273—the company’s prototype vaccine—against Omicron (BA.4/BA.5). Data also revealed that both bivalent vaccines met noninferiority immunogenicity criteria to the original strain.

Stéphane Bancel, Moderna’s CEO, stated, “We are pleased to see that both of our bivalent booster vaccine candidates offer superior protection against Omicron BA.4/BA.5 variants compared to our original booster, which is encouraging given COVID-19 remains a leading cause of hospitalization and death globally. In addition, the superior response against Omicron persisted for at least three months after the mRNA-1273.214 booster. Our bivalent boosters also show, in research assays, neutralizing activity against BQ.1.1, an increasingly dominant emerging variant, confirming that updated vaccines have the potential to offer protection as the virus continues to evolve rapidly to escape our immunity.”

In the phase II/III study, a 50-mcg booster dose of mRNA-1273.222 provoked a superior neutralizing antibody response against Omicron BA.4/BA.5 variants compared with a 50-mcg booster dose of mRNA-1273 in 511 previously vaccinated and boosted participants (ages 19-89 years). Participants received mRNA-1273.222 and mRNA-1273 around 9.5 months and 4.5 months after their prior vaccination, respectively.

Between the mRNA-1273.222 and mRNA-1273 groups, prebooster BA.4/BA.5 titers were comparable. The Omicron BA.4/BA.5 geometric mean titer (GMT) ratios of mRNA-1273.222 versus mRNA-1273 were 5.11 (95% CI: 4.10, 6.36) and 6.29 (95% CI: 5.27, 7.51) for participants with and without SARS-CoV-2 infection prebooster, respectively.

In all participants, the GMT against Omicron BA.4/BA.5 was 4,289 (95% CI: 3,789.0, 4,855.9), representing a 15.1-fold increase (95% CI: 13.3, 17.1) from prebooster levels. For participants without prior infection, the GMT was 2,325 (95% CI: 1321.2, 2812.7), representing a 26.4-fold increase (95% CI: 22.0, 31.9), and for those with prior infection, the GMT was 6,965 (95% CI: 6,043.7, 8,025.4), representing a 9.8-fold (95% CI: 8.4, 11.4) rise from prebooster levels. Significantly, results were consistent between participants aged 65 years and older and those aged 18 to 65 years.

In an exploratory analysis involving an estimated 40 participants utilizing research assays, both bivalent vaccines demonstrated strong neutralizing activity against BQ.1.1, despite an approximately fivefold drop in titers compared with BA.4/BA.5.

As published in the New England Journal of Medicine, researchers indicated that a 50-mcg booster dose of mRNA-1273.214 produced a superior neutralizing antibody response against Omicron BA.1 and Omicron BA.4/BA.5 compared with the booster dose of mRNA-1273, with superiority lasting through at least 3 months. In both groups, participants received the booster dose approximately 4.5 months after prior vaccination.

The occurrence of adverse reactions with mRNA-1273.222 and mRNA-1273.214 were comparable or lower than that of either a second or third dose of the original vaccine. Moreover, no new safety concerns were identified after nearly 1 month and 3 months of follow-up, respectively. These safety and immunogenicity data will be submitted for peer-reviewed publication and shared with regulators globally. These safety data are consistent with those recently published by the CDC and FDA in an analysis of over 211,000 individuals in the v-safe database.

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