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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

Journal article
Authors Staffan Görander
Maria Ekblad
Tomas Bergström
Jan-Åke Liljeqvist
Published in Viruses-Basel
Volume 6
Issue 11
Pages 4358-4372
ISSN 1999-4915
Publication year 2014
Published at Institute of Biomedicine, Department of Infectious Medicine
Pages 4358-4372
Language en
Links dx.doi.org/10.3390/v6114358
Keywords glycoprotein G, herpes simplex virus 2, vaccination, antibodies, GENITAL HERPES, MONOCLONAL-ANTIBODIES, IMMUNE PROTECTION, SUBUNIT, VACCINE, DEFICIENT MICE, GUINEA-PIGS, TYPE-2, INFECTION, HSV-2, IMMUNIZATION
Subject categories Immunology in the medical area

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-gamma. 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.

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