期刊
NATURE
卷 543, 期 7646, 页码 559-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature21435
关键词
-
资金
- National Institutes of Health (NIH) Nonhuman Primate Reagent Resource [HHSN272200900037C, OD10976]
- Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIH)
- Vaccine Research Center of the National Institute of Allergy and Infectious Diseases (NIH)
- National Cancer Institute (NIH) [HHSN261200800001E]
- Collaboration for AIDS Vaccine Discovery grant [OPP1033115]
- NIH Clinical and Translational Science Award (CTSA) program
- NIH Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) [1UM1 AI100663-01]
- Bill and Melinda Gates Foundation [OPP1092074, OPP1124068]
- NIH HIVRAD [P01 AI100148]
- Robertson Foundation
- Bill and Melinda Gates Foundation [OPP1124068, OPP1092074] Funding Source: Bill and Melinda Gates Foundation
Highly potent and broadly neutralizing anti-HIV-1 antibodies (bNAbs) have been used to prevent and treat lentivirus infections in humanized mice, macaques, and humans(1-12). In immunotherapy experiments, administration of bNAbs to chronically infected animals transiently suppresses virus replication, which invariably returns to pre-treatment levels and results in progression to clinical disease. Here we show that early administration of bNAbs in a macaque simian/human immunodeficiency virus (SHIV) model is associated with very low levels of persistent viraemia, which leads to the establishment of T-cell immunity and resultant longterm infection control. Animals challenged with SHIVAD8-EO by mucosal or intravenous routes received a single 2-week course of two potent passively transferred bNAbs (3BNC117 and 10-1074 (refs 13, 14)). Viraemia remained undetectable for 56-177 days, depending on bNAb half-life in vivo. Moreover, in the 13 treated monkeys, plasma virus loads subsequently declined to undetectable levels in 6 controller macaques. Four additional animals maintained their counts of T cells carrying the CD4 antigen (CD4+) and very low levels of viraemia persisted for over 2 years. The frequency of cells carrying replication-competent virus was less than 1 per 106 circulating CD4(+) T cells in the six controller macaques. Infusion of a T-cell-depleting anti-CD8 beta monoclonal antibody to the controller animals led to a specific decline in levels of CD8(+) T cells and the rapid reappearance of plasma viraemia. In contrast, macaques treated for 15 weeks with combination anti-retroviral therapy, beginning on day 3 after infection, experienced sustained rebound plasma viraemia when treatment was interrupted. Our results show that passive immunotherapy during acute SHIV infection differs from combination anti-retroviral therapy in that it facilitates the emergence of potent CD8(+) T-cell immunity able to durably suppress virus replication.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据