Study reveals improved immunogenicity and safety of bivalent Omicron-containing mRNA-1273.214 candidate booster vaccine

In a recent study published in the New England Journal of Medicine, a team of researchers assessed the safety and efficacy of a bivalent candidate vaccine containing spike messenger ribonucleic acids (mRNAs) of the ancestral Wuhan-Hu-1 strain and the Omicron B.1.1.529 [BA.1] variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Study: A Bivalent Omicron-Containing Booster Vaccine against Covid-19. Image Credit: PHOTOCREO Michal Bednarek/Shutterstock


Various SARS-CoV-2 vaccines developed after the onset of the coronavirus disease 2019 (COVID-19) pandemic have been successful in safely and effectively controlling the severity and spread of the disease. Vaccines like the Moderna mRNA-1273 exhibited around 93.2% efficacy after two 100-µg doses during the primary immunization series.

The emergence of SARS-CoV-2 variants such as delta (B.1.617.2) and beta (B.1.351), however, challenged the humoral immunity induced by these vaccines. Recently, the Omicron variant and its subvariants have outcompeted other variants and displayed enhanced immune evasion, courtesy of a combination of new mutations. Studies have shown that the emergent Omicron subvariants show antibody evasion in populations with immunity derived from previous COVID-19 infections, vaccinations, or both.

Therefore, vaccines that induce broader and more potent immune responses are necessary to control the severity of COVID-19. Bivalent vaccines, which stimulate an immune response against two different antigens by combining mRNAs and spike protein fragments, have been shown to elicit stronger and more durable immune responses against different SARS-CoV-2 variants compared to monovalent vaccines.

About the study

In the present study, the researchers compared the immune responses and the adverse reactions induced by a 50-µg dose of the bivalent mRNA-1273.214 vaccine containing mRNAs of the ancestral Wuhan-Hu-1 strain and the Omicron B.1.1.529 [BA.1] variant, and the monovalent mRNA-1273 vaccine that consists of a single mRNA encoding the ancestral SARS-CoV-2 (Wuhan-Hu-1) spike protein.

The team administered the mRNA-1273.214 and mRNA-1273 vaccines as a second booster dose to 437 and 377 participants, respectively, who had received two primary doses of 100-µg and the first booster of a 50-µg mRNA-1273 vaccine.

The safety and reactogenicity were assessed within seven days and 28 days of intramuscular administration of the vaccine. The assessments included immediate local adverse reactions as well as serious adverse events which needed medical attention or led to the discontinuation of the study by the participant.

The immunogenicity was assessed using geometric mean titer ratios. Pseudoviruses carrying SARS-CoV-2 spike proteins from the ancestral (D614G) and Omicron BA.1 variants were used to test the neutralizing antibody titers at 50% inhibitory dilutions (ID50). Additionally, a pseudovirus assay carrying spike proteins from the BA.4 and BA.5 Omicron variants was also employed to test the broad neutralization ability of the vaccine.


The results showed that the bivalent candidate vaccine mRNA-1273.214 had comparable safety and reactogenicity profiles as the mRNA-1273 vaccine. The 50-µg dose of mRNA-1273.214 vaccine elicited fewer adverse events than the 50-µg booster dose and two primary 100-µg doses of the mRNA-1273 vaccine.

The neutralization assays revealed a stronger antibody response against the Omicron variant with the mRNA-1273.214 vaccine compared to the mRNA-1273 vaccine. The immune response against the ancestral SARS-CoV-2 (D614G) strain was similarly superior. The neutralization responses were consistently higher for the mRNA-1273.214 vaccine, notwithstanding previous SARS-CoV-2 infections.

The bivalent mRNA-1273.214 vaccine also displayed better cross-reactivity against multiple variants than the mRNA-1273 vaccine. It elicited neutralizing antibody reactions against the BA.4 and BA.5 Omicron subvariants and presented elevated spike-binding antibody responses against all the other variants irrespective of previous COVID-19 infection.

Previous clinical trials with other bivalent vaccines have displayed durable immune responses six months after vaccination, while clinical trials on the longevity of the present bivalent candidate vaccine are ongoing.

The geometric mean titers against the Omicron BA.1 variant in participants with no history of COVID-19 were 2372.2 and 1473.5 after the administration of the mRNA-1273.214 and mRNA-1273 vaccines, respectively. The mRNA-1273.214 vaccine showed higher geometric mean titers against the Omicron BA.4 and BA.5 variants compared to the mRNA-1273 vaccine. Furthermore, against the alpha, beta, gamma, and delta variants, the bivalent vaccine displayed higher binding antibody responses than the mRNA-1273 booster.


To summarize, the safety and immunogenicity assessments of the bivalent mRNA-1273.214 vaccine containing mRNAs from the Omicron variant and the ancestral Wuhan-Hu-1 strain of SARS-CoV-2 indicate improved neutralization ability against a broad range of variants and reduced adverse reactions to the vaccine.

The longevity of the vaccine and its effectiveness in preventing SARS-CoV-2 infections have not been assessed in the study. However, the findings suggest that with further clinical trials to assess the durability of the vaccine-induced immunity, the bivalent mRNA vaccine could protect against emergent variants.

Journal reference:
  • Chalkias, S., Harper, C., Vrbicky, K., Walsh, S. R., Essink, B., Brosz, A., McGhee, N., Tomassini, J. E., Chen, X., Chang, Y., Sutherland, A., Montefiori, D. C., Girard, B., Edwards, D. K., Feng, J., Zhou, H., Baden, L. R., Miller, J. M., & Das, R. (2022). A Bivalent Omicron-Containing Booster Vaccine against Covid-19. New England Journal of Medicine. doi:

Posted in: Medical Science News | Medical Research News

Tags: Antibody, Assay, Coronavirus, Coronavirus Disease COVID-19, covid-19, Efficacy, Immune Response, immunity, Immunization, Medicine, Omicron, Pandemic, Protein, Pseudovirus, Respiratory, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Spike Protein, Syndrome, Vaccine

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Written by

Dr. Chinta Sidharthan

Chinta Sidharthan is a writer based in Bangalore, India. Her academic background is in evolutionary biology and genetics, and she has extensive experience in scientific research, teaching, science writing, and herpetology. Chinta holds a Ph.D. in evolutionary biology from the Indian Institute of Science and is passionate about science education, writing, animals, wildlife, and conservation. For her doctoral research, she explored the origins and diversification of blindsnakes in India, as a part of which she did extensive fieldwork in the jungles of southern India. She has received the Canadian Governor General’s bronze medal and Bangalore University gold medal for academic excellence and published her research in high-impact journals.

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