Assessment of Two Novel Live-Attenuated Vaccine Candidates for Herpes Simplex Virus 2 (HSV-2) in Guinea Pigs.
Assessment of Two Novel Live-Attenuated Vaccine Candidates for Herpes Simplex Virus 2 (HSV-2) in Guinea Pigs.
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两种新型候选单纯疱疹病毒2 （HSV-2）减毒活疫苗在豚鼠体内的评估
DOI：
10.3390/vaccines9030258
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发表时间：
2021-03-13
期刊：
影响因子：
7.8
通讯作者：
Bertke AS
中科院分区：
文献类型：
--
作者：
Joyce JD;Patel AK;Murphy B;Carr DJJ;Gershburg E;Bertke AS
缓解单纯疱疹病毒2型（HSV-2）感染症状和抑制再活化的治疗方法已有数十年的历史。然而，安全有效的预防或治疗疫苗尚未开发出来。两种新的HSV-2减毒活疫苗候选物（RV201和RV202）已经进行了临床前安全性测试。Hartley豚鼠经阴道（n = 3）或皮内（n = 16）接种任一候选疫苗（2 × 107 PFU），并观察28天的疾病。所有动物均存活至研究结束，未发生HSV-2相关疾病。候选疫苗均未在背根或骶交感神经节中建立潜伏期，如通过病毒DNA定量、LAT表达或外植体再活化所确定。在阴道接种Ryndrome 202后3天，感染性病毒在阴道分泌物中脱落，但Ryndrome 201未脱落，尽管在研究结束时未检测到活性或潜伏的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 × 105 PFU）的豚鼠出现急性疾病、神经系统体征、阴道分泌物中脱落病毒，在整个研究期间出现周期性复发，并在研究结束时在其背根和骶交感神经节中存在潜伏性HSV-2。两种候选疫苗均产生中和抗体。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，应该测试其作为预防性和/或治疗性抗HSV-2疫苗的有效性。
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.
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影响因子：
5.4
作者：
Awasthi, Sita;Zumbrun, Elizabeth E.;Friedman, Harvey M.
通讯作者：
Friedman, Harvey M.
影响因子：
3.7
作者：
Akinyi B;Odhiambo C;Otieno F;Inzaule S;Oswago S;Kerubo E;Ndivo R;Zeh C
通讯作者：
Zeh C
影响因子：
5.4
作者：
Da Costa, X;Kramer, MF;Knipe, DM
通讯作者：
Knipe, DM
影响因子：
4.8
作者：
Dutton, Julie L.;Woo, Wai-Ping;Frazer, Ian H.
通讯作者：
Frazer, Ian H.
DOI：
10.1056/nejmra0807633
发表时间：
2009-10-01
期刊：
The New England journal of medicine
影响因子：
--
作者：
Corey L;Wald A
通讯作者：
Wald A