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Open AccessArticle

Assessment of Two Novel Live-Attenuated Vaccine Candidates for Herpes Simplex Virus 2 (HSV-2) in Guinea Pigs

1
Translational Biology, Medicine and Health, Virginia Polytechnic Institute & State University, Blacksburg, VA 24061, USA
2
Department of Population Health Sciences, Virginia Maryland College of Veterinary Medicine, Virginia Polytechnic Institute & State University, Blacksburg, VA 24061, USA
3
Rational Vaccines, Inc., Cambridge, MA 02139, USA
4
Departments of Microbiology, Immunology, and Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73034, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Ralph A. Tripp
Vaccines 2021, 9(3), 258; https://doi.org/10.3390/vaccines9030258
Received: 14 February 2021 / Revised: 9 March 2021 / Accepted: 10 March 2021 / Published: 13 March 2021
(This article belongs to the Section Attenuated/Inactivated/Live and Vectored Vaccines)
Treatment to ameliorate the symptoms of infection with herpes simplex virus 2 (HSV-2) and to suppress reactivation has been available for decades. However, a safe and effective preventative or therapeutic vaccine has eluded development. Two novel live-attenuated HSV-2 vaccine candidates (RVx201 and RVx202) have been tested preclinically for safety. Hartley guinea pigs were inoculated vaginally (n = 3) or intradermally (n = 16) with either vaccine candidate (2 × 107 PFU) and observed for disease for 28 days. All animals survived to study end without developing HSV-2-associated disease. Neither vaccine candidate established latency in dorsal root or sacral sympathetic ganglia, as determined by viral DNA quantification, LAT expression, or explant reactivation. Infectious virus was shed in vaginal secretions for three days following vaginal inoculation with RVx202, but not RVx201, although active or latent HSV-2 was not detected at study end. In contrast, guinea pigs inoculated with wild-type HSV-2 MS (2 × 105 PFU) vaginally (n = 5) or intradermally (n = 16) developed acute disease, neurological signs, shed virus in vaginal secretions, experienced periodic recurrences throughout the study period, and had latent HSV-2 in their dorsal root and sacral sympathetic ganglia at study end. Both vaccine candidates generated neutralizing antibody. Taken together, these findings suggest that these novel vaccine candidates are safe in guinea pigs and should be tested for efficacy as preventative and/or therapeutic anti-HSV-2 vaccines. View Full-Text
Keywords: herpes simplex virus; HSV-2; vaccine; latency; dorsal root ganglia; guinea pig; immunofluorescence; fluorescent in situ hybridization; explant reactivation; RT-qPCR; qPCR herpes simplex virus; HSV-2; vaccine; latency; dorsal root ganglia; guinea pig; immunofluorescence; fluorescent in situ hybridization; explant reactivation; RT-qPCR; qPCR
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MDPI and ACS Style

Joyce, J.D.; Patel, A.K.; Murphy, B.; Carr, D.J.J.; Gershburg, E.; Bertke, A.S. Assessment of Two Novel Live-Attenuated Vaccine Candidates for Herpes Simplex Virus 2 (HSV-2) in Guinea Pigs. Vaccines 2021, 9, 258. https://doi.org/10.3390/vaccines9030258

AMA Style

Joyce JD, Patel AK, Murphy B, Carr DJJ, Gershburg E, Bertke AS. Assessment of Two Novel Live-Attenuated Vaccine Candidates for Herpes Simplex Virus 2 (HSV-2) in Guinea Pigs. Vaccines. 2021; 9(3):258. https://doi.org/10.3390/vaccines9030258

Chicago/Turabian Style

Joyce, Jonathan D.; Patel, Anant K.; Murphy, Brandie; Carr, Daniel J.J.; Gershburg, Edward; Bertke, Andrea S. 2021. "Assessment of Two Novel Live-Attenuated Vaccine Candidates for Herpes Simplex Virus 2 (HSV-2) in Guinea Pigs" Vaccines 9, no. 3: 258. https://doi.org/10.3390/vaccines9030258

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