Anti-Glycoprotein G Antibodies of Herpes Simplex Virus 2 Contribute to Complete Protection after Vaccination in Mice and Induce Antibody-Dependent Cellular Cytotoxicity and Complement-Mediated Cytolysis

Abstract

We investigated the role of antibodies against the mature portion of glycoprotein G (mgG-2) of herpes simplex virus 2 (HSV-2) in protective immunity after vaccination. Mice were immunized intramuscularly with mgG-2 and oligodeoxynucleotides containing two CpG motifs plus alum as adjuvant. All C57BL/6 mice survived and presented no genital or systemic disease. High levels of immunoglobulin G subclass 1 (IgG1) and IgG2 antibodies were detected and re-stimulated splenic CD4+ T cells proliferated and produced IFN-γ. None of the sera from immunized mice exhibited neutralization, while all sera exerted antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytolysis (ACMC) activity. Passive transfer of anti-mgG-2 monoclonal antibodies, or immune serum, to naive C57BL/6 mice did not limit disease progression. Immunized B‑cell KO mice presented lower survival rate and higher vaginal viral titers, as compared with vaccinated B-cell KO mice after passive transfer of immune serum and vaccinated C57BL/6 mice. Sera from mice that were vaccinated subcutaneously and intranasally with mgG-2 presented significantly lower titers of IgG antibodies and lower ADCC and ACMC activity. We conclude that anti-mgG-2 antibodies were of importance to limit genital HSV‑2 infection. ADCC and ACMC activity are potentially important mechanisms in protective immunity, and could tentatively be evaluated in future animal vaccine studies and in clinical trials.

Vaccination with the Secreted Glycoprotein G of Herpes Simplex Virus 2 Induces Protective Immunity after Genital Infection

“…Initially we compared the intramuscular immunizations with the subcutaneous + intranasal immunizations showing that the intramuscular protocol was significantly better. Similarly, in our earlier report, using mgG-2 as vaccine antigen, the intramuscular administration induced significantly higher survival rate, lower disease scores and higher IgG1, IgG2b and IgG2c antibody levels [ 28 ]. The molecular mechanisms behind these differences are to our knowledge unclear.…”

“…This i.m. protocol was chosen as it has successfully been used in an earlier report using mgG-2 as immunization antigen [ 28 ]. The control groups were immunized with sgG-2 protein without adjuvant, with CpG and alum alone, or with phosphate buffered saline (PBS).…”

Effector mechanisms of humoral immunity to porcine reproductive and respiratory syndrome virus

“…Recent research with both HIV and HSV has shown that ADCC can be directed against non-neutralizing viral antigen targets [37]. Furthermore, this research has suggested that ADCC may be important for prevention of HSV reactivation as well as clearance of HIV infected T lymphocytes [38–40]. Currently, there is no published research examining the role of ADCC in the clearance of PRRSV from infected macrophages.…”

A recombinant plasmid containing CpG motifs as a novel vaccine adjuvant for immune protection against herpes simplex virus 2

“…Mice were intramuscularly immunized with eukaryotic expression plasmids encoding gD to induce protective immune responses (17)(18)(19). Certain immune adjuvants such as interleukin-12, chemokines, cytokines and the E. coli heat labile enterotoxin can enhance the immunogenicity of the HSV DNA vaccine (20)(21)(22)(23).…”