Joyce Jonathan D, Patel Anant K, Murphy Brandie, Carr Daniel J J, Gershburg Edward, Bertke Andrea S
Translational Biology, Medicine and Health, Virginia Polytechnic Institute & State University, Blacksburg, VA 24061, USA.
Department of Population Health Sciences, Virginia Maryland College of Veterinary Medicine, Virginia Polytechnic Institute & State University, Blacksburg, VA 24061, USA.
Vaccines (Basel). 2021 Mar 13;9(3):258. doi: 10.3390/vaccines9030258.
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 ( = 3) or intradermally ( = 16) with either vaccine candidate (2 × 10 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 PFU) vaginally ( = 5) or intradermally ( = 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.
几十年来，一直有用于改善单纯疱疹病毒2型（HSV-2）感染症状和抑制病毒再激活的治疗方法。然而，一种安全有效的预防性或治疗性疫苗的研发却一直未能成功。两种新型减毒活HSV-2候选疫苗（RVx201和RVx202）已在临床前进行了安全性测试。将Hartley豚鼠经阴道（n = 3）或皮内（n = 16）接种任一候选疫苗（2×10⁶ PFU），并观察28天的疾病情况。所有动物均存活至研究结束，未发生与HSV-2相关的疾病。通过病毒DNA定量、LAT表达或外植体重激活测定，两种候选疫苗均未在背根或骶交感神经节中建立潜伏感染。经阴道接种RVx202后，阴道分泌物中排出感染性病毒达三天，但接种RVx201后未出现这种情况，尽管在研究结束时未检测到活跃或潜伏的HSV-2。相比之下，经阴道（n = 5）或皮内（n = 16）接种野生型HSV-2 MS（2×10⁶ PFU）的豚鼠出现了急性疾病、神经症状，阴道分泌物中排出病毒，在整个研究期间经历了周期性复发，并且在研究结束时背根和骶交感神经节中有潜伏的HSV-2。两种候选疫苗均产生了中和抗体。综上所述，这些发现表明这些新型候选疫苗在豚鼠中是安全的，应作为预防性和/或治疗性抗HSV-2疫苗进行疗效测试。
