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 Vaccines

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 3

mRNA vaccine is immunogenic and efficacious in guinea pigs previously infected i.n. with HSV-1.

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mRNA vaccine is immunogenic and efficacious in guinea pigs previously in...
(A) Anti-gG1 ELISA titers from 4 animals prior to HSV-1 infection and 20 animals 1 month after HSV-1. (B) Serum IgG ELISA titers. (C and D) Serum and vaginal neutralizing-antibody titers. (E–K) Survival, genital disease, urinary retention, weight loss, day 2 and day 4 vaginal virus titers, and vaginal shedding of HSV-2 DNA and replication-competent virus days 28 to 48 after infection. Weight loss in H: P = 0.0524 comparing naive and HSV-1+; P = 0.0294 comparing HSV-1+ with HSV-1+ and mRNA; P < 0.0001 comparing naive with HSV-1+ and mRNA. Numbers above the data points in K represent days with HSV-2 shedding and total days sampled. Green symbol indicates that the sample contained replication-competent virus. n = 10 animals/group for B–K, except the naive group in K (n = 1 survivor). P values were calculated by 2-tailed Mann-Whitney test (A–D), log-rank test (E), Kruskal-Wallis test with Dunn’s adjustment for multiple comparisons (F, G, I, and J), Mann-Whitney-Wilcoxon test with Holm’s adjustment for multiple comparisons (H), or 2-tailed Fisher’s exact test (K).