Efficacy of an unmodified bivalent mRNA vaccine against SARS-CoV-2 variants in female small animal models

Nat Commun. 2023 Feb 13;14(1):816. doi: 10.1038/s41467-023-36110-1.

Abstract

Combining optimized spike (S) protein-encoding mRNA vaccines to target multiple SARS-CoV-2 variants could improve control of the COVID-19 pandemic. We compare monovalent and bivalent mRNA vaccines encoding B.1.351 (Beta) and/or B.1.617.2 (Delta) SARS-CoV-2 S-protein in a transgenic mouse and a Wistar rat model. The blended low-dose bivalent mRNA vaccine contains half the mRNA of each respective monovalent vaccine, but induces comparable neutralizing antibody titres, enrichment of lung-resident memory CD8+ T cells, antigen-specific CD4+ and CD8+ responses, and protects transgenic female mice from SARS-CoV-2 lethality. The bivalent mRNA vaccine significantly reduces viral replication in both Beta- and Delta-challenged mice. Sera from bivalent mRNA vaccine immunized female Wistar rats also contain neutralizing antibodies against the B.1.1.529 (Omicron BA.1 and BA.5) variants. These data suggest that low-dose and fit-for-purpose multivalent mRNA vaccines encoding distinct S-proteins are feasible approaches for extending the coverage of vaccines for emerging and co-circulating SARS-CoV-2 variants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • CD8-Positive T-Lymphocytes
  • COVID-19 Vaccines* / immunology
  • COVID-19* / prevention & control
  • Female
  • Mice
  • Mice, Transgenic
  • Models, Animal
  • Rats
  • Rats, Wistar
  • SARS-CoV-2* / genetics
  • Spike Glycoprotein, Coronavirus / genetics
  • Vaccines, Combined / immunology
  • mRNA Vaccines / immunology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • mRNA Vaccines
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Vaccines, Combined

Supplementary concepts

  • SARS-CoV-2 variants