Recombinant adeno-associated virus serotype 9 AAV-RABVG expressing a Rabies Virus G protein confers long-lasting immune responses in mice and non-human primates.
Recombinant adeno-associated virus serotype 9 AAV-RABVG expressing a Rabies Virus G protein confers long-lasting immune responses in mice and non-human primates.
复制标题
表达狂犬病病毒 G 蛋白的重组腺相关病毒血清型 9 AAV-RABVG 赋予小鼠和非人灵长类动物持久的免疫反应
DOI：
10.1080/22221751.2022.2078226
复制
发表时间：
2022-12
影响因子：
13.2
通讯作者：
中科院分区：
文献类型：
--
作者：
人类暴露前或暴露后预防需要三或四剂灭活人狂犬病病毒疫苗肌肉注射。这一程序为防止人类狂犬病死亡做出了巨大贡献，这给发展中国家带来了巨大的经济负担。本文中，产生了携带RABV G基因的重组腺相关病毒血清型9，AAV 9-RABVG，以用作单剂量狂犬病疫苗候选物。AAV 9-RABVG感染293 T细胞后，RABV G蛋白得到稳定表达。2 × 1011 v. p. AAV 9-RABVG单次给药在BALB/c小鼠中诱导了稳健和长期的阳性血清转化，致死性RABV攻击后存活率为100%。食蟹猴单次接种1 × 1013 v. p. AAV 9-RABVG后，狂犬病病毒抗体滴度从免疫后2周开始明显升高，至52周仍维持在31.525IU/ml以上。 更多的DC被激活以有效地呈递RABV G蛋白，更多的B细胞被激活以负责抗体应答。显著更多的RABV G特异性分泌IFN-γ的CD 4+和CD 8 + T细胞以及分泌IL-4的CD 4 + T细胞被激活，并且显著更高水平的IL-2、IFN-γ、IL-4和IL-10被分泌以辅助免疫应答。总体而言，AAV 9-RABVG是单剂量狂犬病疫苗候选物，通过在小鼠和非人灵长类动物中诱导稳健的长期体液应答以及Th 1和Th 2细胞介导的免疫应答而具有巨大前景。
ABSTRACT Three or four intramuscular doses of the inactivated human rabies virus vaccines are needed for pre- or post-exposure prophylaxis in humans. This procedure has made a great contribution to prevent human rabies deaths, which bring huge economic burdens in developing countries. Herein, a recombinant adeno-associated virus serotype 9, AAV9-RABVG, harbouring a RABV G gene, was generated to serve as a single dose rabies vaccine candidate. The RABV G protein was stably expressed in the 293T cells infected with AAV9-RABVG. A single dose of 2 × 1011 v.p. of AAV9-RABVG induced robust and long-term positive seroconversions in BALB/c mice with a 100% survival from a lethal RABV challenge. In Cynomolgus Macaques vaccinated with a single dose of 1 × 1013 v.p. of AAV9-RABVG, the titres of rabies VNAs increased remarkably from 2 weeks after immunity, and maintained over 31.525 IU/ml at 52 weeks. More DCs were activated significantly for efficient antigen presentations of RABV G protein, and more B cells were activated to be responsible for antibody responses. Significantly more RABV G specific IFN-γ-secreting CD4+ and CD8+ T cells, and IL-4-secreting CD4+ T cells were activated, and significantly higher levels of IL-2, IFN-γ, IL-4, and IL-10 were secreted to aid immune responses. Overall, the AAV9-RABVG was a single dose rabies vaccine candidate with great promising by inducing robust, long-term humoral responses and both Th1 and Th2 cell-mediated immune responses in mice and non-human primates.
登录
查看更多内容
AAV-HBV感染的小鼠模型的HBV相关肝纤维化的蛋白质组学和转录组研究。
影响因子：
4.4
作者：
Kan F;Ye L;Yan T;Cao J;Zheng J;Li W
通讯作者：
Li W
影响因子：
5.4
作者：
Jooss, K;Yang, YP;Wilson, JM
通讯作者：
Wilson, JM
影响因子：
5.1
作者：
Li, C.;Narkbunnam, N.;Monahan, P. E.
通讯作者：
Monahan, P. E.
影响因子：
5.8
作者：
Li, Xueling;Cao, Hong;Wang, Lili
通讯作者：
Wang, Lili
影响因子：
6.2
作者：
McGettigan JP
通讯作者：
McGettigan JP