A vaccine containing highly purified virus particles in adjuvant provides high level protection against genital infection and disease in guinea pigs challenged intravaginally with homologous and heterologous strains of herpes simplex virus type 2 |
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| Institution: | 1. Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA;2. Department of Cellular and Molecular Medicine, University of California, San Diego, CA, USA;3. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA, USA;1. UVM Vaccine Testing Center and Department of Pediatrics, University of Vermont Larner College of Medicine, Burlington, VT 05405, USA;2. UVM Vaccine Testing Center and Department of Microbiology and Molecular Genetics, University of Vermont Larner College of Medicine, Burlington, VT 05405, USA;3. Centre for Vaccine Science and Parasitology Lab, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka 1212, Bangladesh;4. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA;5. Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA;6. Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA |
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| Abstract: | Infection with Herpes Simplex Viruses (HSVs) represents a significant health burden worldwide with HSV-1 and HSV-2 causing genital disease and HSV-2 contributing to human immunodeficiency virus acquisition. Despite great need, there is currently no licensed vaccine against HSV. In this report, we evaluated the protective efficacy of a vaccine containing highly purified, inactivated HSV-2 particles (with and without additional recombinant glycoprotein D) formulated with a monophosphoryl lipid A/Alhydrogel adjuvant in a guinea pig HSV genital model. The key results from 3 independent studies were: (1) vaccination consistently provided significant 3–3.5 Log10 reductions in vaginal HSV-2 titers on day 2 postchallenge; (2) following homologous or heterologous challenge with two U.S. isolates, all vaccine groups showed complete protection against lesion formation, significant 3 Log10 reductions in day 2 virus shedding, enhanced virus clearance, significant reductions in HSV-2 DNA within ganglia, and no detectable shedding (<2 PFU) or latent viral DNA in some immunized animals; (3) following challenge with a third heterologous strain, vaccination provided complete protection against primary and recurrent lesions, significant reductions in primary virus shedding, a 50% reduction in recurrent shedding days, and undetectable latent virus in the ganglia and spinal cords of most animals; and (4) adding glycoprotein D provided no enhanced protection relative to that elicited by the inactivated HSV-2 particles alone. Together, these data provide strong support for further development of this exceedingly protective and highly feasible vaccine candidate for human trials. |
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| Keywords: | Genital herpes Herpes simplex virus Vaccine Guinea pigs Inactivated virus adjuvanted vaccine |
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