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

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dc.contributor.authorJoyce, Jonathan D.en
dc.contributor.authorPatel, Anant K.en
dc.contributor.authorMurphy, Brandieen
dc.contributor.authorCarr, Daniel J.J.en
dc.contributor.authorGershburg, Edwarden
dc.contributor.authorBertke, Andrea S.en
dc.contributor.departmentTranslational Biology, Medicine and Healthen
dc.contributor.departmentPopulation Health Sciencesen
dc.date.accessioned2021-03-30T12:39:21Zen
dc.date.available2021-03-30T12:39:21Zen
dc.date.issued2021-03-13en
dc.date.updated2021-03-26T14:05:48Zen
dc.description.abstractTreatment 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 (<i>n</i> = 3) or intradermally (<i>n</i> = 16) with either vaccine candidate (2 × 10<sup>7</sup> 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 × 10<sup>5</sup> PFU) vaginally (<i>n</i> = 5) or intradermally (<i>n</i> = 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.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationJoyce, J.D.; Patel, A.K.; Murphy, B.; Carr, D.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.en
dc.identifier.doihttps://doi.org/10.3390/vaccines9030258en
dc.identifier.urihttp://hdl.handle.net/10919/102876en
dc.language.isoenen
dc.publisherMDPIen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectherpes simplex virusen
dc.subjectHSV-2en
dc.subjectvaccineen
dc.subjectlatencyen
dc.subjectdorsal root gangliaen
dc.subjectguinea pigen
dc.subjectimmunofluorescenceen
dc.subjectfluorescent in situ hybridizationen
dc.subjectexplant reactivationen
dc.subjectRT-qPCRen
dc.subjectqPCRen
dc.titleAssessment of Two Novel Live-Attenuated Vaccine Candidates for Herpes Simplex Virus 2 (HSV-2) in Guinea Pigsen
dc.title.serialVaccinesen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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