Assessment of Two Novel Live-Attenuated Vaccine Candidates for Herpes Simplex Virus 2 (HSV-2) in Guinea Pigs
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-03-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/9/3/258 |
| _version_ | 1797541470137221120 |
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| author | Jonathan D. Joyce Anant K. Patel Brandie Murphy Daniel J.J. Carr Edward Gershburg Andrea S. Bertke |
| author_facet | Jonathan D. Joyce Anant K. Patel Brandie Murphy Daniel J.J. Carr Edward Gershburg Andrea S. Bertke |
| author_sort | Jonathan D. Joyce |
| collection | DOAJ |
| description | 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 (<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. |
| first_indexed | 2024-03-10T13:16:28Z |
| format | Article |
| id | doaj.art-6d72340786054156865c17d0876fa7c1 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T13:16:28Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-6d72340786054156865c17d0876fa7c12023-11-21T10:23:39ZengMDPI AGVaccines2076-393X2021-03-019325810.3390/vaccines9030258Assessment of Two Novel Live-Attenuated Vaccine Candidates for Herpes Simplex Virus 2 (HSV-2) in Guinea PigsJonathan D. Joyce0Anant K. Patel1Brandie Murphy2Daniel J.J. Carr3Edward Gershburg4Andrea S. Bertke5Translational Biology, Medicine and Health, Virginia Polytechnic Institute & State University, Blacksburg, VA 24061, USADepartment of Population Health Sciences, Virginia Maryland College of Veterinary Medicine, Virginia Polytechnic Institute & State University, Blacksburg, VA 24061, USARational Vaccines, Inc., Cambridge, MA 02139, USADepartments of Microbiology, Immunology, and Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73034, USARational Vaccines, Inc., Cambridge, MA 02139, USADepartment of Population Health Sciences, Virginia Maryland College of Veterinary Medicine, Virginia Polytechnic Institute & State University, Blacksburg, VA 24061, USATreatment 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.https://www.mdpi.com/2076-393X/9/3/258herpes simplex virusHSV-2vaccinelatencydorsal root gangliaguinea pig |
| spellingShingle | Jonathan D. Joyce Anant K. Patel Brandie Murphy Daniel J.J. Carr Edward Gershburg Andrea S. Bertke Assessment of Two Novel Live-Attenuated Vaccine Candidates for Herpes Simplex Virus 2 (HSV-2) in Guinea Pigs Vaccines herpes simplex virus HSV-2 vaccine latency dorsal root ganglia guinea pig |
| title | Assessment of Two Novel Live-Attenuated Vaccine Candidates for Herpes Simplex Virus 2 (HSV-2) in Guinea Pigs |
| title_full | Assessment of Two Novel Live-Attenuated Vaccine Candidates for Herpes Simplex Virus 2 (HSV-2) in Guinea Pigs |
| title_fullStr | Assessment of Two Novel Live-Attenuated Vaccine Candidates for Herpes Simplex Virus 2 (HSV-2) in Guinea Pigs |
| title_full_unstemmed | Assessment of Two Novel Live-Attenuated Vaccine Candidates for Herpes Simplex Virus 2 (HSV-2) in Guinea Pigs |
| title_short | Assessment of Two Novel Live-Attenuated Vaccine Candidates for Herpes Simplex Virus 2 (HSV-2) in Guinea Pigs |
| title_sort | assessment of two novel live attenuated vaccine candidates for herpes simplex virus 2 hsv 2 in guinea pigs |
| topic | herpes simplex virus HSV-2 vaccine latency dorsal root ganglia guinea pig |
| url | https://www.mdpi.com/2076-393X/9/3/258 |
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