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/...

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Main Authors: Staffan Görander, Maria Ekblad, Tomas Bergström, Jan-Åke Liljeqvist
Format: Article
Language:English
Published: MDPI AG 2014-11-01
Series:Viruses
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Online Access:http://www.mdpi.com/1999-4915/6/11/4358
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author Staffan Görander
Maria Ekblad
Tomas Bergström
Jan-Åke Liljeqvist
author_facet Staffan Görander
Maria Ekblad
Tomas Bergström
Jan-Åke Liljeqvist
author_sort Staffan Görander
collection DOAJ
description 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.
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spelling doaj.art-0eb9ea5090324395aa816ce0a46b76532022-12-22T03:53:17ZengMDPI AGViruses1999-49152014-11-016114358437210.3390/v6114358v6114358Anti-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 CytolysisStaffan Görander0Maria Ekblad1Tomas Bergström2Jan-Åke Liljeqvist3Department 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, SwedenDepartment 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, SwedenDepartment 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, SwedenDepartment 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, SwedenWe 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.http://www.mdpi.com/1999-4915/6/11/4358glycoprotein Gherpes simplex virus 2vaccinationantibodies
spellingShingle Staffan Görander
Maria Ekblad
Tomas Bergström
Jan-Åke Liljeqvist
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
Viruses
glycoprotein G
herpes simplex virus 2
vaccination
antibodies
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic glycoprotein G
herpes simplex virus 2
vaccination
antibodies
url http://www.mdpi.com/1999-4915/6/11/4358
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