Immunity induced by DNA immunization with herpes simplex virus type 2 glycoproteins B and C

• Published in: Vaccine 1999-12, Vol.18 (9), p.875-883
• Main Authors: Mester, Joseph C, Twomey, Tara A, Tepe, Eric T, Bernstein, David I
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cercopithecus aethiops; Disease Models, Animal; DNA immunization; DNA vaccines; Enzyme-Linked Immunosorbent Assay; Experimental viral diseases and models; Female; Fundamental and applied biological sciences. Psychology; Genital herpes; glycoprotein B; glycoprotein C; Guinea Pigs; Herpes Genitalis - prevention & control; herpes simplex virus 2; HSV vaccine; Infectious diseases; Medical sciences; Mice; Microbiology; Plasmids; Rabbits; Simplexvirus - genetics; Simplexvirus - immunology; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, DNA; Vagina - virology; Vero Cells; Viral diseases; Viral Envelope Proteins - genetics; Viral Envelope Proteins - immunology; Virology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/S0264-410X(99)00325-4

The complete sequence of herpes simplex virus type 2 (HSV-2) glycoproteins B and C (gB & gC) were cloned into plasmid expression vectors and evaluated in murine and guinea pig genital HSV-2 models. Balb/c mice were immunized with either pgB-2 or pgC-2 plasmids intramuscularly (IM) or intradermally (ID). The vaccines induced HSV-2-specific neutralizing and ELISA IgG antibody, but little or no enhancement of viral clearance from the vagina was detected following intravaginal challenge. Immunization of guinea pigs with pgB-2 or pgC-2 induced ELISA IgG antibody; however, antibody titers were approximately one log 10 unit lower than that seen in HSV-2 convalescent sera. IM immunization of guinea pigs with either plasmid also did not decrease vaginal viral shedding following vaginal challenge, but the severity of the acute disease and the subsequent number of recurrent lesion days were reduced in animals immunized with pgB-2. Lastly, IM immunization of latently infected guinea pigs with a combined gB-2 and gC-2 plasmid vaccine significantly reduced the number of subsequent HSV-2 recurrences. DNA vectors expressing gB-2 or gC-2 were both immunogenic, although the gB-2 plasmid induced higher titers of antibody and significantly reduced primary and recurrent herpetic disease in the guinea pig model. These results also suggest that immunotherapy with plasmid expression vectors may be effective against recurrent genital HSV-2 disease.