当前位置: X-MOL 学术bioRxiv. Immunol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Long term sterile immunity induced by an adjuvant-containing live-attenuated AIDS virus
bioRxiv - Immunology Pub Date : 2020-05-26 , DOI: 10.1101/2020.05.22.111781
Tomotaka Okamura , Yuya Shimizu , Tomohiro Kanuma , Yusuke Tsujimura , Masamitsu N Asaka , Kazuhiro Matsuo , Takuya Yamamoto , Yasuhiro Yasutomi

Antigen 85B (Ag85B) is one of the most dominant proteins secreted from most mycobacterial species, and it induces Th1-type immune responses as an adjuvant. We genetically constructed a live attenuated simian human immunodeficiency virus to express the adjuvant molecule Ag85B (SHIV-Ag85B). SHIV-Ag85B could not be detected 4 weeks after injection in cynomolgus macaques, and strong SHIV-specific T cell responses were induced in these macaques. When these macaques in which SHIV-Ag85B had become undetectable were challenged with pathogenic SHIV89.6P at 37 weeks after SHIV-Ag85B became undetectable, SHIV89.6P could not be detected after the challenge. Eradication of SHIV89.6P was confirmed by adoptive transfer experiments and CD8-depletion studies. The SHIV-Ag85B-inoculated macaques showed enhancement of Gag-specific monofunctional and polyfunctional CD8+ T cells in the acute phase of pathogenic SHIV challenge. The results suggest that SHIV-Ag85B elicited strong sterile immune responses against pathogenic SHIV and that it may lead to the development of a vaccine for AIDS virus infection.

中文翻译:

含佐剂的减毒活病毒诱导的长期无菌免疫

抗原85B(Ag85B)是大多数分枝杆菌物种分泌的最主要的蛋白质之一,它可以诱导Th1型免疫应答作为佐剂。我们通过遗传构建了减毒的猿猴活免疫缺陷病毒,以表达佐剂分子Ag85B(SHIV-Ag85B)。猕猴猕猴注射后4周无法检测到SHIV-Ag85B,并且在这些猕猴中诱导了强烈的SHIV特异性T细胞应答。当无法检测到SHIV-Ag85B的这些猕猴在无法检测到SHIV-Ag85B后的37周用致病性SHIV89.6P攻击时,在攻击后无法检测到SHIV89.6P。通过过继转移实验和CD8耗竭研究证实了SHIV89.6P的根除。接种SHIV-Ag85B的猕猴显示Gag特异性单功能和多功能CD8增强+ T细胞在致病性SHIV感染的急性期。结果表明,SHIV-Ag85B引发了针对病原性SHIV的强烈的无菌免疫反应,这可能导致开发出艾滋病病毒感染疫苗。
更新日期:2020-05-26
down
wechat
bug