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

文献类型： 外文期刊

第一作者： Shi, Chenjuan

作者： Shi, Chenjuan;Tian, Li;Zheng, Wenwen;Zhu, Yelei;Liu, Lele;Liu, Wenkai;Song, Yanyan;Zheng, Xuexing;Zhu, Yelei;Sun, Peilu;Xia, Xianzhu;Xue, Xianghong;Xia, Xianzhu

作者机构：

关键词： Adeno-associated virus serotype 9; rabies virus; glycoprotein; vaccine; neutralizing antibodies

期刊名称：EMERGING MICROBES & INFECTIONS （ 影响因子：19.568； 五年影响因子：14.211 ）

ISSN：

年卷期： 2022 年 11 卷 1 期

页码：

收录情况： SCI

摘要： 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 x 10(11) 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 x 10(13) 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-gamma-secreting CD4+ and CD8+ T cells, and IL-4-secreting CD4+ T cells were activated, and significantly higher levels of IL-2, IFN-gamma, 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.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序