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-γ (IFN-γ) 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-γ 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.
Highlights
Herpes simplex virus 2 (HSV-2) infects the genital mucosa and establishes latency with life-long infection in sensory dorsal root ganglia
The sgG-2 protein was purified from the medium of virus-infected GMK-AH1 cells and subjected
We show that vaccination with native sgG‐2 combined with cytosine-phosphate-guanine dinucleotide (CpG) and alum given
Summary
Herpes simplex virus 2 (HSV-2) infects the genital mucosa and establishes latency with life-long infection in sensory dorsal root ganglia. Frequent viral reactivation of HSV-2 induces recurrent genital disease or, more often, asymptomatic shedding of the virus [1,2,3]. In new-born and in immunocompromised patients, the HSV-2 infection can elicit severe and often fatal central nervous system infection. HSV-2 infection significantly increases the risk of acquiring human immunodeficiency virus (HIV) [5]. A prophylactic vaccine would be the best means to decrease HSV-2-related morbidity. No vaccine is approved and clinical trials using the glycoprotein B (gB) and/or glycoprotein D (gD) have failed to protect against HSV-2 infection or disease [6,7].
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