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- Title
Broad protection and respiratory immunity of dual mRNA vaccination against SARS-CoV-2 variants.
- Authors
Hajnik, Renee L.; Plante, Jessica A.; Reddy Bonam, Srinivasa; Rafael, Grace H.; Liang, Yuejin; Hazell, Nicholas C.; Walker, Jordyn; Reyna, Rachel A.; Walker, David H.; Alameh, Mohamad-Gabriel; Weissman, Drew; Weaver, Scott C.; Plante, Kenneth S.; Hu, Haitao
- Abstract
While first-generation, spike (S)-based COVID-19 vaccines were effective against early SARS-CoV-2 strains, the rapid evolution of novel Omicron subvariants have substantially reduced vaccine efficacy. As such, broadly protective vaccines against SARS-CoV-2 are needed to prevent future viral emergence. In addition, it remains less clear whether peripheral immunization, especially with mRNA vaccines, elicits effective respiratory immunity. Our group has developed a nucleoside-modified mRNA vaccine expressing the nucleocapsid (N) protein of the ancestral SARS-CoV-2 virus and has tested its use in combination with the S-based mRNA vaccine (mRNA-S). In this study, we examined efficacy of mRNA-N alone or in combination with mRNA-S (mRNA-S+N) against more immune evasive Omicron variants in hamsters. Our data show that mRNA-N alone induces a modest but significant protection against BA.5 and that dual mRNA-S+N vaccination confers complete protection against both BA.5 and BQ.1, preventing detection of virus in the hamster lungs. Analysis of respiratory immune response in mice shows that intramuscular mRNA-S+N immunization effectively induces respiratory S- and N-specific T cell responses in the lungs and in bronchoalveolar lavage (BAL), as well as antigen-specific binding IgG in BAL. Together, our data further support mRNA-S+N as a potential pan-COVID-19 vaccine for broad protection against current and emerging SARS-CoV-2 variants.
- Subjects
SARS-CoV-2; SARS-CoV-2 Omicron variant; VACCINATION; MESSENGER RNA; VACCINE effectiveness; FC receptors
- Publication
NPJ Vaccines, 2024, Vol 9, Issue 1, p1
- ISSN
2059-0105
- Publication type
Article
- DOI
10.1038/s41541-024-00957-2