Bivalent SARS-CoV-2 mRNA vaccines increase breadth of neutralization and protect against the BA.5 Omicron variant in mice
Open accessAbstract
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in the Omicron lineage has resulted in diminished Coronavirus Disease 2019 (COVID-19) vaccine efficacy and persistent transmission. In this study, we evaluated the immunogenicity and protective efficacy of two, recently authorized, bivalent COVID-19 vaccines that contain two mRNAs encoding Wuhan-1 and either BA.1 (mRNA-1273.214) or BA.4/5 (mRNA-1273.222) spike proteins. As a primary two-dose immunization series in mice, both bivalent vaccines induced greater neutralizing antibody responses against Omicron variants than the parental, monovalent mRNA-1273 vaccine. When administered to mice as a booster at 7 months after the primary vaccination series with mRNA-1273, the bivalent vaccines induced broadly neutralizing antibody responses. Whereas most anti-Omicron receptor binding domain antibodies in serum induced by mRNA-1273, mRNA-1273.214 and mRNA-1273.222 boosters cross-reacted with the antecedent Wuhan-1 spike antigen, the mRNA-1273.214 and mRNA-1273.222 bivalent vaccine boosters also induced unique BA.1-specific and BA.4/5-specific responses, respectively. Although boosting with parental or bivalent mRNA vaccines substantially improved protection against BA.5 compared to mice receiving two vaccine doses, the levels of infection, inflammation and pathology in the lung were lowest in animals administered the bivalent mRNA vaccines. Thus, boosting with bivalent Omicron-based mRNA-1273.214 or mRNA-1273.222 vaccines enhances immunogenicity and confers protection in mice against a currently circulating SARS-CoV-2 strain.
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Modified bivalent mRNA SARS-CoV-2 vaccines elicited significantly higher nAb responses against recent SARS-CoV-2 variants and non-inferior titres against ancestral virus compared with monovalent vaccines in humans and preclinical animal models.
“In addition, modified bivalent mRNA SARS-CoV-2 vaccines elicited significantly higher nAb responses against recent SARS-CoV-2 variants and non-inferior titres against ancestral virus compared with monovalent vaccines in humans and preclinical animal models9,24.”
From Efficacy of an unmodified bivalent mRNA vaccine against SARS-CoV-2 variants in female small animal models (2023) · cites this paper as [9]
The Results sections on preclinical vaccination and boosting report stronger neutralization of Omicron variants by bivalent vaccines than by ancestral monovalent mRNA-1273 in mice. The study did not test humans; the Discussion only says its findings are consistent with human serum data from other studies. It also does not establish non-inferiority of ancestral-virus titres, and notes that some variant comparisons did not reach statistical significance. Page numbers are unavailable in our copy. (LLM, conf=0.88)
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- Authors
- Scheaffer, S. M., Lee, D., Whitener, B., Ying, B., Wu, K., Liang, C.-Y., Jani, H., Martin, P., Amato, N. J., Avena, L. E., Berrueta, D. M., Schmidt, S. D., O’Dell, S., Nasir, A., Chuang, G.-Y., Stewart-Jones, G., Koup, R. A., Doria-Rose, N. A., Carfi, A., Elbashir, S. M., Thackray, L. B., Edwards, D. K., & Diamond, M. S.
- Affiliations
- Washington University in St. Louis (US)
- Moderna Therapeutics (United States) (US)
- National Institute of Allergy and Infectious Diseases (US)
- Corresponding author
- Elbashir, Sayda M.
- Thackray, Larissa B.
- Edwards, Darin K.
- Diamond, Michael S.
- ORCID
- Venue
- Nature Medicine
- Published
- 2022-10-20
- Volume
- 29
- Issue
- 1
- Pages
- 247-257
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC11752949
- OpenAlex
- W4306874674
- Cited by
- 169
- References
- 56
- Citations by year
- 2026: 10 · 2025: 25 · 2024: 56 · 2023: 68 · 2022: 10
- FWCI
- 19.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (R01 AI157155, HHSN272201400008C, 75N93021C00014, 75N93019C00051)
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- bivalent mRNA vaccine, Omicron variant, BA.5, BA.1, neutralizing antibodies, booster vaccination, cross-reactivity, receptor binding domain, lung pathology, COVID-19 vaccine efficacy
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, mRNA Vaccines, 2019-nCoV Vaccine mRNA-1273, Animals, Antibodies, Viral, Humans, RNA, Messenger, Vaccines, Combined, Mice, Antibodies, Neutralizing
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