期刊
NATURE MEDICINE
卷 22, 期 7, 页码 762-770出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.4105
关键词
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资金
- Simian Vaccine Evaluation Unit (SVEU) [HHSN266200600005C]
- intramural US National Cancer Institute (NCI) program
- extramural US National Institute of Allergy and Infectious Diseases (NIAID) program
- US Army Medical Research and Material Command (USAMRMC) [W81XWH-07-2-0067]
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.
- US Department of Defense
- Collaboration for AIDS Vaccine Discovery (CAVD) grants from the Bill and Melinda Gates Foundation [OPP1032325, OPP1032817]
- NCI
- US National Institutes of Health (NIH) [HHSN261200800001E]
- NIH [HHSN27201100016C]
- Center for AIDS Research [AI064518]
- Bill and Melinda Gates' Foundation [OPP111572]
- NIH/NIAID [5R01AI102691]
- Intramural Research Program of the Vaccine Research Center, NIAID, NIH
- CAVD from the Bill and Melinda Gates Foundation [OPP1032325, R01 AI118581, R01 AI102715]
A recombinant vaccine containing Aventis Pasteur's canarypox vector (ALVAC)-HIV and gp120 alum. decreased the risk of HIV acquisition in the RV144 vaccine trial. The substitution, of alum with the more immunogenic MF59 adjuvant is under consideration for the next efficacy human trial. We found here that an ALVAC-simian immunodeficiency virus (SIV) and gp120 alum (ALVAC-SIV + gp120) equivalent vaccine, but not an ALVAC-SIV + gp120 MF59 vaccine, was efficacious in delaying the onset of SIVmac251 in rhesus macaques, despite the higher immunogenicity of the latter adjuvant. Vaccine efficacy was associated with alum-induced, but not with MF59-induced, envelope (Env)-dependent mucosal innate lymphoid cells (ILCs) that produce interleukin (IL)-17, as well as with mucosal IgG to the gp120 variable region 2 (V2) and the expression of 12 genes, ten of which are part of the RAS pathway. The association between RAS activation and vaccine efficacy was also observed in an independent efficacious SIV-vaccine approach. Whether RAS activation, mucosal ILCs and antibodies to V2 are also important hallmarks of HIV-vaccine efficacy in humans will require further studies.
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