Vaccine targeting SIVmac251 protease cleavage sites protects macaques against vaginal infection
| dc.contributor.author | Li, Hongzhao | |
| dc.contributor.author | Omange, Were | |
| dc.contributor.author | Liang, Binhua | |
| dc.contributor.author | Toledo, Nikki | |
| dc.contributor.author | Hai, Yan | |
| dc.contributor.author | Liu, Lewis | |
| dc.contributor.author | Schalk, Dane | |
| dc.contributor.author | Crecente-Campo, Jose | |
| dc.contributor.author | Dacoba, Tamara | |
| dc.contributor.author | Lambe, Andrew | |
| dc.contributor.author | Lim, So-Yon | |
| dc.contributor.author | Kashem, Mohammad | |
| dc.contributor.author | Wan, Yanmin | |
| dc.contributor.author | Correia-Pinto, Jorge | |
| dc.contributor.author | Seaman, Michael | |
| dc.contributor.author | Liu, Xiao | |
| dc.contributor.author | Balshaw, Robert | |
| dc.contributor.author | Li, Qingsheng | |
| dc.contributor.author | Schultz-Darken, Nancy | |
| dc.contributor.author | Alonso, Maria | |
| dc.contributor.author | Plummer, Francis | |
| dc.contributor.author | Whitney, James | |
| dc.contributor.author | Luo, Ma | |
| dc.date.accessioned | 2021-08-12T16:57:04Z | |
| dc.date.available | 2021-08-12T16:57:04Z | |
| dc.date.issued | 2020-11-03 | |
| dc.date.submitted | 2021-08-12T02:48:10Z | en_US |
| dc.description.abstract | After over 3 decades of research, an effective anti-HIV vaccine remains elusive. The recently halted HVTN702 clinical trial not only further stresses the challenge to develop an effective HIV vaccine but also emphasizes that unconventional and novel vaccine strategies are urgently needed. Here, we report that a vaccine focusing the immune response on the sequences surrounding the 12 viral protease cleavage sites (PCSs) provided greater than 80% protection to Mauritian cynomolgus macaques against repeated intravaginal SIVmac251 challenges. The PCS-specific T cell responses correlated with vaccine efficacy. The PCS vaccine did not induce immune activation or inflammation known to be associated with increased susceptibility to HIV infection. Machine learning analyses revealed that the immune microenvironment generated by the PCS vaccine was predictive of vaccine efficacy. Our study demonstrates, for the first time to our knowledge, that a vaccine which targets only viral maturation, but lacks full-length Env and Gag immunogens, can prevent intravaginal infection in a stringent macaque/SIV challenge model. Targeting HIV maturation thus offers a potentially novel approach to developing an effective HIV vaccine. | en_US |
| dc.description.sponsorship | This work was supported by an NIH grant (R01AI111805), a CIHR/CHVI bridge grant, and funding from the National Microbiology Laboratory, Public Health Agency of Canada. Research reported in this publication was supported in part by the Office of the Director, NIH, under award number P51OD011106 to the Wisconsin National Primate Research Center, University of Wisconsin-Madison. This research was conducted (or conducted in part) at a facility constructed with support from Research Facilities Improvement Program grant numbers RR15459-01 and RR020141-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. | en_US |
| dc.identifier.citation | Li H et al.(2020). J Clin Invest.;130(12):6429-6442. https://doi.org/10.1172/JCI13872 | en_US |
| dc.identifier.doi | org/10.1172/JCI138728 | |
| dc.identifier.uri | http://hdl.handle.net/1993/35801 | |
| dc.language.iso | eng | en_US |
| dc.publisher | Journal of Clinical Investigation | en_US |
| dc.rights | open access | en_US |
| dc.subject | Vaccine | en_US |
| dc.subject | Protease cleavage sites | en_US |
| dc.subject | macaques | en_US |
| dc.subject | vaginal infection | en_US |
| dc.subject | Monkeys | en_US |
| dc.title | Vaccine targeting SIVmac251 protease cleavage sites protects macaques against vaginal infection | en_US |
| dc.type | Article | en_US |
| local.author.affiliation | Rady Faculty of Health Sciences | en_US |