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

Journal article
Authors Karin Önnheim
Maria Ekblad
Staffan Görander
Tomas Bergström
Jan-Åke Liljeqvist
Published in Viruses-Basel
Volume 8
Issue 4
ISSN 1999-4915
Publication year 2016
Published at Institute of Biomedicine, Department of Infectious Medicine
Language en
Links dx.doi.org/10.3390/v8040110
Keywords secreted glycoprotein G, herpes simplex virus 2, vaccination, type-2 infection, monoclonal-antibodies, subunit vaccine, human-sera, b-cells, hsv-2, mice, antigen, identification, efficacy, Virology
Subject categories Virology, Infectious Medicine

Abstract

Herpes simplex virus 2 (HSV-2) infects the genital mucosa and establishes a life-long infection in sensory ganglia. After primary infection HSV-2 may reactivate causing recurrent genital ulcerations. HSV-2 infection is prevalent, and globally more than 400 million individuals are infected. As clinical trials have failed to show protection against HSV-2 infection, new vaccine candidates are warranted. The secreted glycoprotein G (sgG-2) of HSV-2 was evaluated as a prophylactic vaccine in mice using two different immunization and adjuvant protocols. The protocol with three intramuscular immunizations combining sgG-2 with cytosine-phosphate-guanine dinucleotide (CpG) motifs and alum induced almost complete protection from genital and systemic disease after intra-vaginal challenge with HSV-2. Robust immunoglobulin G (IgG) antibody titers were detected with no neutralization activity. Purified splenic CD4+ T cells proliferated and produced interferon-gamma (IFN-gamma) when re-stimulated with the antigen in vitro. sgG-2 + adjuvant intra-muscularly immunized mice showed a significant reduction of infectious HSV-2 and increased IFN-gamma levels in vaginal washes. The HSV-2 DNA copy numbers were significantly reduced in dorsal root ganglia, spinal cord, and in serum at day six or day 21 post challenge. We show that a sgG-2 based vaccine is highly effective and can be considered as a novel candidate in the development of a prophylactic vaccine against HSV-2 infection.

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