SARS-CoV-2 bivalent mRNA vaccine with broad protection against variants of concern

Front Immunol. 2023 May 24:14:1195299. doi: 10.3389/fimmu.2023.1195299. eCollection 2023.

Abstract

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has rapidly spread around the globe. With a substantial number of mutations in its Spike protein, the SARS-CoV-2 Omicron variant is prone to immune evasion and led to the reduced efficacy of approved vaccines. Thus, emerging variants have brought new challenges to the prevention of COVID-19 and updated vaccines are urgently needed to provide better protection against the Omicron variant or other highly mutated variants.

Materials and methods: Here, we developed a novel bivalent mRNA vaccine, RBMRNA-405, comprising a 1:1 mix of mRNAs encoding both Delta-derived and Omicron-derived Spike proteins. We evaluated the immunogenicity of RBMRNA-405 in BALB/c mice and compared the antibody response and prophylactic efficacy induced by monovalent Delta or Omicron-specific vaccine with the bivalent RBMRNA-405 vaccine in the SARSCoV-2 variant challenge.

Results: Results showed that the RBMRNA-405 vaccine could generate broader neutralizing antibody responses against both Wuhan-Hu-1 and other SARS-CoV-2 variants, including Delta, Omicron, Alpha, Beta, and Gamma. RBMRNA-405 efficiently blocked infectious viral replication and lung injury in both Omicron- and Delta-challenged K18-ACE2 mice.

Conclusion: Our data suggest that RBMRNA-405 is a promising bivalent SARS-CoV-2 vaccine with broad-spectrum efficacy for further clinical development.

Keywords: SARS-CoV-2; bivalent mRNA vaccine; broad-spectrum efficacy; immunogenicity; variants of concern (VOCs).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COVID-19 Vaccines*
  • COVID-19* / prevention & control
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • RNA, Messenger
  • SARS-CoV-2
  • Vaccines, Combined
  • mRNA Vaccines

Substances

  • COVID-19 Vaccines
  • RNA, Messenger
  • Vaccines, Combined
  • mRNA Vaccines

Supplementary concepts

  • SARS-CoV-2 variants

Grants and funding

This work was supported by the Emergency Key Program of Guangzhou Laboratory (EKPG21-06, EKPG21-22), the Young Top Talent of Science and Technology Innovation Department of Guangdong Province (2021TQ060189), the Guangdong Provincial Research Project for Prevention and Treatment of SARS-CoV-2 (2021A1111090003), the Guangzhou Science and Technology Planning Project (202102100003), the Guangdong Provincial Department of Natural Resources Project (GDNRC [2021]51), the Youth Lift Project of China Association for Science and Technology (2020-2022QNRC002), the Guizhou Natural Science Foundation ([2020]4Y219), and the Guangdong Basic and Applied Basic Research Foundation (2020B1515120045 and 2020A1515110151).