Development and immunogenicity evaluation in mice of a novel mRNA vaccine expressing herpes simplex virus type 2 envelope glycoprotein gD.

Jialuo BING; Liye JIN; Yao DENG; Shucai SUN; Xiaotian HAN; Xueting CHENG; Zhenyong QI; Tangqi WANG; Ruiwen HAN; Desheng ZHAI; Wenjie TAN

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Development and immunogenicity evaluation in mice of a novel mRNA vaccine expressing herpes simplex virus type 2 envelope glycoprotein gD.

Author: Jialuo BING ¹ ; Liye JIN ¹ ; Yao DENG ² ; Shucai SUN ² ; Xiaotian HAN ² ; Xueting CHENG ² ; Zhenyong QI ¹ ; Tangqi WANG ² ; Ruiwen HAN ² ; Desheng ZHAI ¹ ; Wenjie TAN ²
Author Information

1. School of Public Health, Xinxiang Medical University, Xinxiang 453003, Henan, China.
2. National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
Publication Type:Journal Article
Keywords: envelope glycoprotein gD; herpes simplex virus type 2; immune response; lipopolyplex; mRNA vaccine
MeSH: Animals; Herpesvirus 2, Human/genetics*; Viral Envelope Proteins/genetics*; Mice; Herpes Genitalis/immunology*; RNA, Messenger/immunology*; Female; Mice, Inbred BALB C; Antibodies, Viral/blood*; mRNA Vaccines/immunology*; Antibodies, Neutralizing/blood*; Humans
From: Chinese Journal of Biotechnology 2025;41(8):3241-3251
CountryChina
Language:Chinese
Abstract: Human alphaherpesvirus 2 (HSV-2) is the main pathogen resulting human genital herpes, which poses a major threat to the socio-economic development, while there is no effective vaccine. In this study, we developed a novel lipopolyplex (LPP)-delivered mRNA vaccine expressing the HSV-2 envelope glycoprotein gD and evaluated its immunogenicity in mice. The mRNA vaccine was prepared from the genetically modified gD mRNA synthesized in vitro combined with the LPP delivery platform and it was named gD-ORI mRNA. The expression of gD antigen in the mRNA vaccine was validated in vitro by Western blotting and indirect immunofluorescence assay, then the immune responses induced by this mRNA vaccine in mice were evaluated. The immunization with gD mRNA alone induced strong humoral and cellular immune responses in mice. Robust and long-lasting gD-specific IgG antibodies were detected in the mouse serum after booster immunization with gD-ORI mRNA. The immunized mice exhibited a Th1/Th2 balanced IgG response and robust neutralizing antibodies against HSV-2, and a clear dose-response relationship was observed. The gD-specific IgG antibodies were maintained in mice for a long time, up to 18 weeks post-booster immunization. At the same time, multifunctional gD-specific CD4⁺ and CD8⁺ T cells in vaccinated mice were detected by intracellular cytokine staining (ICS). This novel gD-expressing mRNA vaccine delivered by LPP induces strong and long-lasting immune responses in mice post booster immunization and has a promising prospect for development and application. This study provides scientific evidence and reference for the development of a new mRNA vaccine for HSV-2.