Journal
IMMUNITY
Volume 50, Issue 1, Pages 241-+Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2018.11.011
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Funding
- NIAID [UM1AI100663]
- Bill & Melinda Gates Foundation [OPP1084519, OPP1145046]
- National Institutes of Health [AI121135, AI136621, AI124377, AI126603, AI128751, OD011106]
- CIHR [352417]
- Canada Research Chair on Retroviral Entry [RCHS0235]
- National Institute of Allergy and Infectious Diseases [R00AI120851, UM1AI068618]
- Translational Virology Core at the UC San Diego Center for AIDS Research [P30 AI036214]
- IGM Genomics Center, University of California, San Diego, La Jolla, California
- NIH [Al131873]
- Achievement Rewards for College Scientists Foundation
- Bill and Melinda Gates Foundation [OPP1145046, OPP1084519] Funding Source: Bill and Melinda Gates Foundation
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Passive administration of HIV neutralizing antibodies (nAbs) can protect macaques from hard-to-neutralize (tier 2) chimeric simian-human immunodeficiency virus (SHIV) challenge. However, conditions for nAb-mediated protection after vaccination have not been established. Here, we selected groups of 6 rhesus macaques with either high or low serum nAb titers from a total of 78 animals immunized with recombinant native-like (SOSIP) Env trimers. Repeat intrarectal challenge with homologous tier 2 SHIVBG505 led to rapid infection in unimmunized and low-titer animals. High-titer animals, however, demonstrated protection that was gradually lost as nAb titers waned over time. An autologous serum ID50 nAb titer of similar to 1:500 afforded more than 90% protection from medium-dose SHIV infection. In contrast, antibody-dependent cellular cytotoxicity and T cell activity did not correlate with protection. Therefore, Env protein-based vaccination strategies can protect against hard-to-neutralize SHIV challenge in rhesus macaques by inducing tier 2 nAbs, provided appropriate neutralizing titers can be reached and maintained.
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