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 6

Tfh cell, gD2-specific GC B cell, and memory B cell responses are more potent for the mRNA than the protein vaccine in mice.

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Tfh cell, gD2-specific GC B cell, and memory B cell responses are more p...
(A) Tfh response on day 17 after 1 immunization with mRNA, protein, or poly(C) as a control. (B) gD2+ B cells on day 17. (C) Percentage gD2+ B cells with GC phenotype on day 17. (D–F) Tfh cells, gD2+ B cells, and percentage gD2+ B cells with GC phenotype 40 days after 1 immunization. (G) Frequency of CD80 and PD-L2 expression in gD2+ memory (GL7–CD38+) B cells on day 40. (H) gD2+ B cells 1 year after 2 mRNA or 3 protein immunizations. (I) Frequency of CD80 and PD-L2 expression in gD2+ memory B cells at 1 year. (J) IgG1, IgG2a, and IgG2b anti-gD2 antibody-secreting cells (ASCs) at 1 year detected by ELISpot. P values were calculated by ordinary 1-way ANOVA (A, B, D, E, H, and J) or unpaired t test (C and F).