![]() Although whole HSV-2 vaccines appear to be more effective than glycoprotein subunit vaccines, we lack a cohesive explanation as to why this should be the case. Likewise, several whole HSV-2 vaccine approaches including dl-529, cJ2-gD2, and killed HSV-2 + alum/MPL adjuvant elicit superior protection against HSV-2 in animal models relative to gD-2 subunit vaccines. In side-by-side comparisons, a live HSV-2 ICP0 - mutant virus, HSV-2 0ΔNLS, elicited up to 100-times greater protection against HSV-2 genital herpes in mice and guinea pigs relative to animals immunized with a gD-2 subunit vaccine. The same is true of HSV-2 ICP0 - mutant viruses. Our interest in the approach stemmed from the fact that HSV-1 ICP0 - mutant viruses are exquisitely sensitive to repression by the innate interferon-α/β response, and thus are profoundly attenuated in severe-combined immunodeficient (SCID) hosts. Our laboratory has investigated the potential of a live HSV-2 ICP0 - mutant virus to address the unmet need for an effective HSV-2 vaccine. Six clinical trials of HSV-2 glycoprotein D (gD-2) and/or glycoprotein B (gB-2) subunit vaccines have been conducted over the past 25 years, but have failed to prevent or reduce the symptoms of HSV-2 genital herpes. Glycoprotein subunit vaccines represent the most widely studied approach to develop a safe and effective HSV-2 vaccine. Hence, it is widely agreed that an effective HSV-2 vaccine is an important and unmet medical need. Wild-type HSV-2 may cause severe infections in neonates, and HSV-2-infected individuals are placed at ~3-fold higher risk for acquiring human immunodeficiency virus. Herpes simplex virus 2 (HSV-2) infects more than 530 million people worldwide between the ages of 14 and 49, and >20 million individuals live with genital herpes disease that recurs more than once a year. This does not alter the authors’ adherence to all PLOS ONE policies on sharing data and materials. ![]() The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: William Halford is a co-author on United States Patent Number 8,802,109, which describes the uses of herpes simplex virus mutant ICP0 in the design of a live-attenuated HSV-2 vaccine strain. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedĭata Availability: All relevant data are within the paper and its Supporting Information files.įunding: This work was supported by the Excellence in Academic Medicine Committee of the Southern Illinois University School of Medicine, as well as a grant from the National Institutes of Health to study the Development of an Effective Genital Herpes Vaccine (R21 AI81072). Received: JAccepted: DecemPublished: February 6, 2015Ĭopyright: © 2015 Geltz et al. This increased breadth of antibody-generating proteins may contribute to the live HSV-2 vaccine’s capacity to elicit superior protection against genital herpes relative to a gD subunit vaccine.Ĭitation: Geltz JJ, Gershburg E, Halford WP (2015) Herpes Simplex Virus 2 (HSV-2) Infected Cell Proteins Are among the Most Dominant Antigens of a Live-Attenuated HSV-2 Vaccine. Collectively, the results suggest the immune response to the live HSV-2 0ΔNLS vaccine includes antibodies specific for infected cell proteins, capsid proteins, tegument proteins, and glycoproteins. Mass spectrometry suggested 44% of immunoprecipitated viral peptides were derived from two HSV-2 infected cells proteins, RR-1 and ICP8, whereas only 14% of immunoprecipitated peptides were derived from HSV-2’s thirteen glycoproteins. Immunoprecipitation (IP) of total HSV-2 antigen with 0ΔNLS antiserum pulled down 19 viral proteins. Many antibodies were directed against infected-cell proteins of >100 kDa in size, and only 10 ± 5% of antibodies were directed against gD. Western blot analyses indicated the live HSV-2 0ΔNLS vaccine elicited an IgG antibody response against 9 or more viral proteins. In light of these results, we sought to determine which viral proteins were the dominant antibody-generators (antigens) of the live HSV-2 0ΔNLS vaccine. We have observed that mice immunized with a live HSV-2 ICP0 - mutant virus, HSV-2 0ΔNLS, are 10 to 100 times better protected against genital herpes than mice immunized with a HSV-2 gD subunit vaccine ( PLoS ONE 6:e17748). Virion glycoproteins such as glycoprotein D (gD) are believed to be the dominant antigens of herpes simplex virus 2 (HSV-2).
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