Bivalent SARS-CoV-2 Vaccine Might Offer Better Omicron Protection


Interim data show a bivalent vaccine that contains the Omicron variant may be more effective.

bivalent booster

A bivalent booster vaccine against COVID-19 that contains the Omicron variant appears to provide superior protection against the variant without additional safety concerns, according to new interim data.

The report adds evidence to the case that bivalent vaccines may be a meaningful tool as public health officials plan their long-term ongoing responses to COVID-19. The results were published in the New England Journal of Medicine.

Corresponding author Spyros Chalkias, MD, of Moderna said while the company’s initial mRNA-1273 vaccine has been highly effective against COVID-19, the SARS-CoV-2 virus has continued to evolve and new variants have posed new challenges.

Booster doses of mRNA-1273 have been shown to improve neutralizing antibody responses against new variants, Chalkias and colleagues wrote.
“Nonetheless, the vaccine effectiveness against Omicron is lower than that against other variants, and second booster doses of Omicron-containing vaccines have been authorized in the United States."

In the ongoing phase 2/3 study, which was funded by Moderna, investigators wanted to see how well a bivalent formulation of the 50-μg mRNA-1273 booster might perform compared to the original. The bivalent version—called mRNA-1273.214—includes 2 mRNAs, one containing the ancestral SARS-CoV-2 virus and one containing the Omicron variant BA.1. The study’s primary objective is to evaluate the shot’s safety and reactogenicity.

All participants in the study had received the original 2-dose (100-μg) primary vaccination series with mRNA-1273, along with a 50-μg booster dose at least 3 months prior to the start of the study. Patients were then randomized to receive either a second booster of mRNA-1273 (377 participants) or a dose of mRNA-1273.214, the omicron-containing booster (437 participants). The 2 groups had similar time between their first and second boosters (median of 136 days in the mRNA-1273.214 group and 134 days in the mRNA-1273 group).

Chalkias and colleagues said the Omicron-containing booster appeared to lead to stronger results.

“In participants with no previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the geometric mean titers of neutralizing antibodies against the Omicron BA.1 variant were 2372.4 (95% confidence interval [CI], 2070.6 to 2718.2) after receipt of the mRNA-1273.214 booster and 1473.5 (95% CI, 1270.8 to 1708.4) after receipt of the mRNA-1273 booster,” they reported.

The mRNA-1273.214 vaccine also led to higher neutralizing antibodies against the BA.4 and BA.5 variants, and against alpha, beta, delta, and gamma variants of SARS-CoV-2. Safety results were similar between the 2 booster groups, the investigators said.

Last month, the FDA authorized the use of mRNA-1273.214 as a booster shot.

As of the cutoff for the interim results, 20 people in the study had become infected with SARS-CoV-2, including 11 in the mRNA-1273.214 group, but the authors said this study was not designed to evaluate vaccine efficacy. Instead, they wanted to verify the booster shot’s safety and see how the antibody responses it sparked compared with the previously approved vaccine. In that regard, they said, the data so far are promising, though the exact mechanism behind that superior response is not yet fully known.

“These results are consistent with the evaluation of our bivalent beta-containing vaccine, which induced enhanced and durable antibody responses,” Chalkias and colleagues concluded. “Together, these findings indicate that bivalent vaccines may be a new tool in the response to emerging variants.”


Chalkias S, Harper C, Vrbicky K, et al. A Bivalent Omicron-Containing Booster Vaccine against Covid-19 [published online ahead of print, 2022 Sep 16]. N Engl J Med. 2022;10.1056/NEJMoa2208343. doi:10.1056/NEJMoa2208343

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