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Bivalent SARS-CoV-2 mRNA vaccines increase breadth of neutralization and protect against the BA.5 Omicron variant in
Suzanne M Scheaffer1, Diana Lee2, Bradley Whitener1
1Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Abstract:
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.
Insights
New bivalent COVID-19 vaccines (mRNA-1273.214 and mRNA-1273.222) show enhanced immunogenicity and protection against Omicron variants in mice. Boosting with these vaccines improved neutralizing antibody responses and reduced lung pathology compared to older vaccines.
Area of Science:
- Immunology
- Vaccinology
- Virology
Background:
- Emergence of SARS-CoV-2 Omicron variants reduced COVID-19 vaccine effectiveness.
- Bivalent vaccines targeting ancestral and Omicron strains were developed.
Purpose of the Study:
- Evaluate immunogenicity and protective efficacy of two bivalent mRNA vaccines (mRNA-1273.214 and mRNA-1273.222).
- Compare bivalent vaccines to the original monovalent mRNA-1273 vaccine.
Main Methods:
- Mice received primary two-dose immunization or a booster seven months after primary vaccination.
- Neutralizing antibody responses, cross-reactivity, and protection against SARS-CoV-2 variants were assessed.
Main Results:
- Bivalent vaccines induced greater neutralizing antibody responses against Omicron variants than the monovalent vaccine.
- Bivalent boosters elicited broadly neutralizing antibodies and unique variant-specific responses.
- Boosting with bivalent vaccines significantly improved protection and reduced lung inflammation and pathology.
Conclusions:
- Bivalent Omicron-based mRNA vaccines enhance immunogenicity and confer protection against current SARS-CoV-2 strains.
- These vaccines represent a promising strategy to combat evolving variants and persistent COVID-19 transmission.
