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Glycoprotein G of Herpes Simplex Virus 2 as a Novel Vaccine Antigen for Immunity to Genital and Neurological Disease

Journal article
Authors Staffan Görander
Ali M Harandi
Madelene Lindqvist
Tomas Bergström
Jan-Åke Liljeqvist
Published in Journal of Virology
Volume 86
Issue 14
Pages 7544-7553
ISSN 0022-538X
Publication year 2012
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Institute of Biomedicine, Department of Infectious Medicine
Pages 7544-7553
Language en
Links dx.doi.org/10.1128/jvi.00186-12
Keywords dependent cellular cytotoxicity, monoclonal-antibodies, type-2, infection, ifn-gamma, intranasal immunization, vaginal infection, hsv-2, infection, t-cells, b-cells, mice
Subject categories Infectious Medicine

Abstract

The envelope glycoproteins of herpes simplex virus 1 (HSV-1) and HSV-2, with the exception of glycoprotein G, elicit cross-reactive B- and T-cell responses. Human vaccine trials, using the cross-reactive glycoproteins B and D, have shown no protection against genital HSV-2 infection or disease. In this study, the mature form of glycoprotein G (mgG-2) of HSV-2 was used for immunization of mice, either alone or in combination with adjuvant CpG, followed by an intravaginal challenge with a lethal dose of a fully virulent HSV-2 strain. Mice immunized with mgG-2 plus CpG showed low disease scores and a significantly higher survival rate (73%) than mice immunized with mgG-2 alone (20%) or controls (0%). Accordingly, limited numbers of infectious HSV-2 particles were detected in the spinal cord of mice immunized with mgG-2 plus CpG. The observed protection was associated with a gamma interferon (IFN-gamma) response by splenic CD4(+) T cells upon antigen restimulation in vitro and in vaginal washes 1 day postinfection. The majority of sera collected from mice immunized with mgG-2 plus CpG showed macrophage-mediated antibody-dependent cellular cytotoxicity and antibody-dependent complement-mediated cytolysis, while no neutralization activity was observed. In conclusion, we have shown that immunization with the type-specific mgG-2 protein in combination with CpG could elicit protective immunity against an otherwise lethal vaginal HSV-2 challenge. The mgG-2 protein may therefore constitute a promising HSV-2 vaccine antigen to be considered for future human trials.

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