Intramuscular vaccination of mice with the human herpes simplex virus type-1(HSV-1) VC2 vaccine, but not its parental strain HSV-1 (F) confers full protection against lethal ocular HSV-1 (McKrae) pathogenesis
Intramuscular vaccination of mice with the human herpes simplex virus type-1(HSV-1) VC2 vaccine, but not its parental strain HSV-1 (F) confers full protection against lethal ocular HSV-1 (McKrae) pathogenesis
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DOI：
10.1371/journal.pone.0228252
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发表时间：
2020-02-06
期刊：
影响因子：
3.7
通讯作者：
Kousoulas, Konstantin G.
中科院分区：
文献类型：
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作者：
Naidu, Shan K.;Nabi, Rafiq;Kousoulas, Konstantin G.
1 型单纯疱疹病毒 (HSV-1) 可导致严重的眼部感染和失明。我们之前已经证明，HSV-1 VC2 疫苗株对小鼠和豚鼠在 HSV-1 或 HSV-2 阴道攻击后具有保护作用，防止生殖器疱疹感染。在这项研究中，我们评估了小鼠接受致命人类临床毒株 HSV-1 (McKrae) 眼部攻击后，肌肉注射 VC2 疫苗对抗疱疹性角膜炎的功效。与亲本毒株 HSV-1(F) 相比，接种 VC2 疫苗对小鼠产生了更好的保护和发病控制。具体而言，在 HSV-1(McKrae) 眼部攻击后，所有 VC2 疫苗接种的小鼠均存活，而 30% 的 HSV-1(F) 疫苗接种小鼠和 100% 的模拟疫苗接种小鼠在攻击后死亡。接种VC2的小鼠没有表现出任何眼部感染症状，并且从最初的结膜炎中完全恢复。相比之下，HSV-1（F）疫苗接种的小鼠出现以角膜混浊为特征的时间依赖性进行性角膜炎，而模拟疫苗接种的动物则表现出更严重的基质性角膜炎，其特征是角膜基质中免疫细胞浸润和新生血管形成并伴有角膜混浊。与模拟组或 HSV-1(F) 接种组相比，VC2 免疫小鼠的角膜表现出 CD3+ T 淋巴细胞浸润显着增加，Iba1+ 巨噬细胞浸润减少。攻击后，VC2 免疫产生比 HSV-1(F) 更高的病毒中和滴度。此外，在眼部 HSV-1 (McKrae) 攻击、然后模拟或 HSV-1(F) 疫苗接种后，VC 疫苗接种显着增加了引流淋巴结中的 CD4 T 中央记忆 (TCM) 亚群和 CD8 T 效应记忆 (TEM) 亚群。这些结果表明，VC2 疫苗接种在攻击部位产生保护性免疫反应，以防止 HSV-1 诱导的眼部发病。
Herpes simplex virus type-1 (HSV-1) can cause severe ocular infection and blindness. We have previously shown that the HSV-1 VC2 vaccine strain is protective in mice and guinea pigs against genital herpes infection following vaginal challenge with HSV-1 or HSV-2. In this study, we evaluated the efficacy of VC2 intramuscular vaccination in mice against herpetic keratitis following ocular challenge with lethal human clinical strain HSV-1(McKrae). VC2 vaccination in mice produced superior protection and morbidity control in comparison to its parental strain HSV-1(F). Specifically, after HSV-1(McKrae) ocular challenge, all VC2 vaccinated-mice survived, while 30% of the HSV-1(F)-vaccinated and 100% of the mock-vaccinated mice died post challenge. VC2-vaccinated mice did not exhibit any symptoms of ocular infection and completely recovered from initial conjunctivitis. In contrast, HSV-1(F)-vaccinated mice developed time-dependent progressive keratitis characterized by corneal opacification, while mockvaccinated animals exhibited more severe stromal keratitis characterized by immune cell infiltration and neovascularization in corneal stroma with corneal opacification. Cornea in VC2immunized mice exhibited significantly increased infiltration of CD3+ T lymphocytes and decreased infiltration of Iba1+ macrophages in comparison to mock-or HSV-1(F)-vaccinated groups. VC2 immunization produced higher virus neutralization titers than HSV-1(F) post challenge. Furthermore, VC-vaccination significantly increased the CD4 T central memory (TCM) subsets and CD8 T effector memory (TEM) subsets in the draining lymph nodes following ocular HSV-1 (McKrae) challenge, then mock-or HSV-1(F)-vaccination. These results indicate that VC2 vaccination produces a protective immune response at the site of challenge to protect against HSV-1-induced ocular pathogenesis.