期刊
VACCINES
卷 9, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/vaccines9030258
关键词
herpes simplex virus; HSV-2; vaccine; latency; dorsal root ganglia; guinea pig; immunofluorescence; fluorescent in situ hybridization; explant reactivation; RT-qPCR; qPCR
资金
- Rational Vaccines Inc.
- National Institutes of Health [R01 AI053108]
The study showed that the two novel live-attenuated HSV-2 vaccine candidates are safe in guinea pigs and do not establish latency in neural ganglia. In contrast, wild-type HSV-2 resulted in acute disease and latent infection in neural ganglia. Both vaccine candidates elicited neutralizing antibodies.
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 x 10(7) 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 x 10(5) 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.
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