Trivalent nucleoside-modified mRNA vaccine yields durable memory B cell protection against genital herpes in preclinical models
Sita Awasthi, … , Gary H. Cohen, Harvey M. Friedman
Sita Awasthi, … , Gary H. Cohen, Harvey M. Friedman
Published October 7, 2021
Citation Information: J Clin Invest. 2021;131(23):e152310. https://doi.org/10.1172/JCI152310.
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Research Article Infectious disease

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

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Figure 1

Serum and vaginal antibody titers in guinea pigs.

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Serum and vaginal antibody titers in guinea pigs. (A) Anti-gC2, -gD2, an...
(A) Anti-gC2, -gD2, and -gE2 serum IgG ELISA titers of naive (unimmunized) animal samples obtained 5 months after entering the animal colony or mRNA- and protein-immunized animals 1 or 8 months after the final immunization. (B and C) Serum and vaginal fluid neutralizing-antibody titers 1 or 8 months after the final immunization. n = 10/group for naive, protein at 1 month, and protein at 8 months; n = 20 for mRNA at 1 month and mRNA at 8 months. P values were calculated by 2-tailed Mann-Whitney test for gC2 and gD2 ELISA, and by Kruskal-Wallis test with Dunn’s correction for multiple comparisons for gE2 ELISA, serum, and vaginal neutralizing titers.