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.
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.
Department of Infectious Diseases, Section of Virology, Guldhedsgatan 10 B, S-413 46 Gothenburg, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Box 100, 405 30 Göteborg, Sweden. staffan.gorander@gu.se.
Staffan
S
Görander
Department of Infectious Diseases, Section of Virology, Guldhedsgatan 10 B, S-413 46 Gothenburg, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Box 100, 405 30 Göteborg, Sweden. maria.ekblad@microbio.gu.se.
Maria
M
Ekblad
Department of Infectious Diseases, Section of Virology, Guldhedsgatan 10 B, S-413 46 Gothenburg, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Box 100, 405 30 Göteborg, Sweden. tomas.bergstrom@microbio.gu.se.
Tomas
T
Bergström
Department of Infectious Diseases, Section of Virology, Guldhedsgatan 10 B, S-413 46 Gothenburg, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Box 100, 405 30 Göteborg, Sweden. jan-ake.liljeqvist@gu.se.
Jan-Åke
JÅ
Liljeqvist
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D000920:Antibody-Dependent Cell Cytotoxicity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D003165:Complement System Proteins; D005260:Female; D006561:Herpes Simplex / Q000276:immunology / Q000517:prevention & control; D022301:Herpes Simplex Virus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000378:metabolism; D008810:Mice, Inbred C57BL; D016019:Survival Analysis; D014759:Viral Envelope Proteins / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D022301:Herpes Simplex Virus Vaccines; D007074:Immunoglobulin G; D014759:Viral Envelope Proteins; C045464:glycoprotein G, herpes simplex virus type 2; D007371:Interferon-gamma; D003165:Complement System Proteins