Trivalent nucleoside-modified mRNA vaccine yields durable memory B cell protection against genital herpes in preclinical models.

Abstract

Nucleoside-modified mRNA vaccines have gained global attention because of COVID-19. We evaluated a similar vaccine approach for preventing a chronic, latent genital infection rather than an acute respiratory infection. We used animal models to compare an HSV-2 trivalent nucleoside-modified mRNA vaccine with the same antigens prepared as proteins, with an emphasis on antigen-specific memory B cell responses and immune correlates of protection. In guinea pigs, serum neutralizing-antibody titers were higher at 1 month and declined far less by 8 months in mRNA- compared with protein-immunized animals. Both vaccines protected against death and genital lesions when infected 1 month after immunization; however, protection was more durable in the mRNA group compared with the protein group when infected after 8 months, an interval representing greater than 15% of the animal's lifespan. Serum and vaginal neutralizing-antibody titers correlated with protection against infection, as measured by genital lesions and vaginal virus titers 2 days after infection. In mice, the mRNA vaccine generated more antigen-specific memory B cells than the protein vaccine at early times after immunization that persisted for up to 1 year. High neutralizing titers and robust B cell immune memory likely explain the more durable protection by the HSV-2 mRNA vaccine.

• Authors: Sita Awasthi, James J Knox, Angela Desmond, Mohamad-Gabriel Alameh, Brian T Gaudette, John M Lubinski, Alexis Naughton, Lauren M Hook, Kevin P Egan, Ying K Tam, Norbert Pardi, David Allman, Eline T Luning Prak, Michael P Cancro, Drew Weissman, Gary H Cohen, Harvey M Friedman
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 131 Issue 23 (12 01 2021) ISSN: 1558-8238 [Electronic] United States
• PMID: 34618692 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• RNA, Viral
• Vaccines, Synthetic
• Viral Vaccines

Topics

• Animals
• COVID-19 (immunology, prevention & control)
• Disease Models, Animal
• Female
• Guinea Pigs
• Herpes Genitalis (immunology, prevention & control)
• Herpesvirus 2, Human (immunology)
• Immunologic Memory
• Memory B Cells (immunology)
• RNA, Viral (immunology)
• SARS-CoV-2 (immunology)
• Vaccines, Synthetic (immunology)
• Viral Vaccines (immunology)
• mRNA Vaccines