New Bivalent Omicron-Containing Booster Vaccine May Elicit Higher Antibody Response Against COVID-19


Patients could have a better immune response against the omicron variant of COVID-19 with a second booster of the bivalent mRNA-1273.214 vaccine at a 50 μg dose.

As a booster, the 50 μg (microgram) bivalent omicron-containing vaccine mRNA-1273.214 (Moderna) was found to have a superior neutralizing antibody response as compared to the mRNA-1273 vaccine (Moderna) at the same dose.

The mRNA-1273.214 vaccine contains bivalent omicron BA.1. It was found to have a safe reactogenicity profile, as did the original 50-μg mRNA-1273 booster vaccine.

“When administered as a second booster, a 50-μg dose of the bivalent omicron BA.1–containing mRNA-1273.214 vaccine had a safety and reactogenicity profile that was similar to that of the prototype 50-μg mRNA-1273 booster vaccine,” wrote the study authors in their report published in the New England Journal of Medicine.

The 50-μg mRNA-1273 is approved in the United States to protect against COVID-19, but it was found to be less effective against the omicron variant. The mRNA-1273-214 bivalent vaccine is unique in that it contains 2 mRNAs to defend against 2 variants (the ancestral and omicron BA.1), and research indicates bivalent vaccines could be more effective against multiple strains of COVID-19.

Researchers aimed to identify the safety and immunogenicity of the 50-μg bivalent vaccine mRNA-1273.214 as a booster against the authorized mRNA-1273 vaccine of the same dose. The primary endpoint was to assess safety, reactogenicity, and immunogenicity of the mRNA-1273.214 booster dose after 28 days. The key secondary endpoint compared the 50-μg dose of mRNA-1273.214 to a 50-μg dose of the mRNA-1273 vaccine and defined as noninferiority against the ancestral SARS-CoV-2 virus at 28 days following a second booster.

The study enrolled patients who already received 2 primary doses of 100 μg mRNA-1273 and a 50 μg booster of the mRNA-1273 vaccine—437 patients were given the mRNA-1273.214 as a second booster and 377 patients were given the mRNA-1273.

The investigators followed-up with participants on day 29 at the interim analysis. Compared to the original mRNA-1273 vaccine, the mRNA-1273.214 vaccine showed to have a more effective neutralizing antibody response against the omicron variant—along with subvariant strains of omicron, including the BA.4/5. Neutralizing antibody response can determine COVID-19 efficacy.

“Neutralizing antibody responses were consistently higher with mRNA-1273.214 than with mRNA-1273, irrespective of previous SARSCoV-2 infection,” study authors wrote in their report.

Further, the authors suggest that a successful booster could be a significant way to boost immune response against omicron amongst vaccinated individuals and previously infected individuals because data suggest that the vaccines could lose their efficacy against omicron.

The bivalent omicron-containing 50-μg mRNA-1273.214 vaccine also offered more protection against the original SARS-CoV-2 virus. Administered as a booster, the 50-μg dose of the mRNA-1273.214 vaccine closely matched the safety reactogenicity profile of the 50-μg dose of mRNA-1273 at 28 days.

The study was not randomized, which could limit the results. Additionally, the study assessed humoral immune responses, but not cellular. This led researchers to recommend collecting data that can support the mRNA-1273.214 vaccine for multiple responses. Finally, the vaccine was not measured for efficacy, which would need to be evaluated in a future study.

“These findings indicate that bivalent vaccines may be a new tool in the response to emerging variants,” study authors said in the report.


Chalkias, Spyros, Harper, Charles, Vrbicky, Keith, et al. A Bivalent Omicron-Containing Booster Vaccine against Covid-19. The New England Journal of Medicine. Accessed September 26, 2022.

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