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.
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

To determine the characteristics of seroprevalence of herpes simplex virus type 2 (HSV-2) infection among Korean people, a cross-sectional study was conducted on three groups in 2004. The three groups consisted of the general public who visited public health centers, commercial sex workers (CSWs), and human immunodeficiency virus (HIV)-infected persons. Among the general public, HSV-2 seroprevalence rates for age under the 20s, in the 20s, 30s, 40s and the above 22.6%, 32.7% and 32.3%, respectively, which showed rapid increase of the rate in the 30s (p<0.0001). In case of the above of 19 yr old, women (28.0%) was higher than men (21.7%) (p<0.0001). The rate of CSWs (81.6%) was about 10 times higher than that of general women. In case of HIV-infected men (47.6%), the figure was about 2-3 times higher than that of general men. The low rate in the teens and the 20s proved that it is essential to develop sexually transmitted infections (STIs) prevention programs of education and publicity for them as a precaution measure. This study is the first major study of its kind on HSV-2 and would provide basic data for prevention of STIs including information about target groups subject to vaccination program.
Adult ; Age Factors ; Aged ; Antibodies, Viral/*blood ; Female ; HIV Infections/complications ; Herpes Genitalis ; Herpesvirus 2, Human/*immunology ; Humans ; Korea/epidemiology ; Male ; Middle Aged ; Seroepidemiologic Studies