A Trivalent HSV-2 gC2, gD2, gE2 Nucleoside-Modified mRNA-LNP Vaccine Provides Outstanding Protection in Mice against Genital and Non-Genital HSV-1 Infection, Comparable to the Same Antigens Derived from HSV-1.

Article

作者: Fowler, Bernard T ; Cohen, Gary H ; Beattie, Mitchell ; Weissman, Drew ; Egan, Kevin P ; Naughton, Alexis M ; Awasthi, Sita ; Hook, Lauren M ; Tebaldi, Giulia ; Friedman, Harvey M ; Alameh, Mohamad-Gabriel

HSV-1 disease is a significant public health burden causing orofacial, genital, cornea, and brain infection. We previously reported that a trivalent HSV-2 gC2, gD2, gE2 nucleoside-modified mRNA-lipid nanoparticle (LNP) vaccine provides excellent protection against vaginal HSV-1 infection in mice. Here, we evaluated whether this HSV-2 gC2, gD2, gE2 vaccine is as effective as a similar HSV-1 mRNA LNP vaccine containing gC1, gD1, and gE1 in the murine lip and genital infection models. Mice were immunized twice with a total mRNA dose of 1 or 10 µg. The two vaccines produced comparable HSV-1 neutralizing antibody titers, and surprisingly, the HSV-2 vaccine stimulated more potent CD8⁺ T-cell responses to gE1 peptides than the HSV-1 vaccine. Both vaccines provided complete protection from clinical disease in the lip model, while in the genital model, both vaccines prevented death and genital disease, but the HSV-1 vaccine reduced day two vaginal titers slightly better at the 1 µg dose. Both vaccines prevented HSV-1 DNA from reaching the trigeminal or dorsal root ganglia to a similar extent. We conclude that the trivalent HSV-2 mRNA vaccine provides outstanding protection against HSV-1 challenge at two sites and may serve as a universal prophylactic vaccine for HSV-1 and HSV-2.

2023-01-31·Journal of Virology

Nucleoside-Modified mRNA-Based Influenza Vaccines Circumvent Problems Associated with H3N2 Vaccine Strain Egg Adaptation

Article

作者: Furey, Colleen ; Fan, Steven H. Y. ; Hensley, Scott E. ; Weissman, Drew ; Gouma, Sigrid ; Parkhouse, Kaela ; Santos, Jefferson J. S. ; Pardi, Norbert ; Weirick, Madison ; Muramatsu, Hiromi

This study shows that the nucleoside-modified mRNA-LNP vaccine platform is a promising alternative for egg-based influenza vaccines. We show that mRNA-LNP vaccines expressing H3 antigens elicit high levels of antibodies in mice and protect against H3N2 influenza virus infection.

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适应症	最高研发状态	国家/地区	公司	日期
流感病毒感染	临床前	全球	National Institute For Health & Care Research	2022-12-14
流感病毒感染	临床前	全球	Acuitas Therapeutics, Inc.	2022-12-14