Author: Luning Prak, Eline T ; Friedman, Harvey M ; Cohen, Gary H ; Weissman, Drew ; Hook, Lauren M ; Desmond, Angela ; Knox, James J ; Lubinski, John M ; Tam, Ying K ; Alameh, Mohamad-Gabriel ; Gaudette, Brian T ; Cancro, Michael P ; Awasthi, Sita ; Egan, Kevin P ; Naughton, Alexis ; Allman, David ; Pardi, Norbert

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.

Vaccines

Immunogenicity and Protective Efficacy of an mRNA Vaccine Targeting HSV-2 UL41 in Mice

Article

Author: Jia, Jie ; Li, Shao-You ; Kuang, Yi-Qun ; Gao, Kai-Cheng ; Mou, Tangwei ; Zhao, Yu

Background: Herpes simplex virus 2 (HSV-2) is the primary cause of sexually transmitted genital ulcerative diseases, for which no effective prophylactic vaccine is currently available. However, the identification of appropriate targets for an HSV-2 mRNA vaccine remains an area requiring further investigation. Methods: The immunogenicity and protective effects of an HSV-2 UL41 mRNA vaccine were evaluated in a BALB/c mouse model. The mice were intramuscularly immunized twice, followed by HSV-2 infection at 28 days post boost. Clinical signs were monitored daily, and the viral load and tissue inflammation were assessed on days 1, 4, and 7 post infection. Dendritic cell (DC) activation in spleen tissue was analyzed via transcriptome sequencing. Results: A comparison of the clinical, immunological, and pathological characteristics of the groups that were immunized with the UL41 mRNA vaccine and then infected with HSV2, along with the control groups, revealed that the vaccine elicited both cellular and humoral immunity, inhibited viral replication, suppressed the inflammatory response, and provided protective effects against the virus in vivo. Furthermore, in vitro assays of DC expansion revealed that the vaccine immunization increased the induction of DCs from splenic cells. Transcriptomic analysis of these DCs revealed the activation of immune signaling pathways. Conclusions: Our study suggests that the UL41 mRNA vaccine may provide effective protection against HSV-2-related diseases and holds promise as a potential mRNA vaccine candidate.

100 Deals associated with HSV-2 mRNA vaccine (Perelman School of Medicine)

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Indication	Highest Phase	Country/Location	Organization	Date
Herpes Simplex	Preclinical	United States	Perelman School of Medicine	-
Herpes Simplex	Preclinical	Germany	BioNTech SE	-

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HSV-2 mRNA vaccine (Perelman School of Medicine)

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