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

Autor:	Awasthi S; Infectious Disease Division, Department of Medicine and., Knox JJ; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Desmond A; Infectious Disease Division, Department of Medicine and.; Infectious Disease Division, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Alameh MG; Infectious Disease Division, Department of Medicine and., Gaudette BT; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Lubinski JM; Infectious Disease Division, Department of Medicine and., Naughton A; Infectious Disease Division, Department of Medicine and., Hook LM; Infectious Disease Division, Department of Medicine and., Egan KP; Infectious Disease Division, Department of Medicine and., Tam YK; Acuitas Therapeutics Inc., Vancouver, British Columbia, Canada., Pardi N; Infectious Disease Division, Department of Medicine and., Allman D; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Luning Prak ET; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Cancro MP; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Weissman D; Infectious Disease Division, Department of Medicine and., Cohen GH; Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Friedman HM; Infectious Disease Division, Department of Medicine and.
Jazyk:	angličtina
Zdroj:	The Journal of clinical investigation [J Clin Invest] 2021 Dec 01; Vol. 131 (23).
DOI:	10.1172/JCI152310
Abstrakt:	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.
Databáze:	MEDLINE
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