Vaccine-induced protection from homologous tier 2 SHIV challenge in nonhuman primates depends on serum-neutralizing antibody titers.

Authors: Pauthner, Matthias G and Nkolola, Joseph P and Havenar-Daughton, Colin and Murrell, Ben and Reiss, Samantha M and Bastidas, Raiza and Prévost, Jérémie and Nedellec, Rebecca and von Bredow, Benjamin and Abbink, Peter and Cottrell, Christopher A and Kulp, Daniel W and Tokatlian, Talar and Nogal, Bartek and Bianchi, Matteo and Li, Hui and Lee, Jeong Hyun and Butera, Salvatore T and Evans, David T and Hangartner, Lars and Finzi, Andrés and Wilson, Ian A and Wyatt, Richard T and Irvine, Darrell J and Schief, William R and Ward, Andrew B and Sanders, Rogier W and Crotty, Shane and Shaw, George M and Barouch, Dan H and Burton, Dennis R

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 ~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. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Journal: Immunity
DOI: 10.1016/j.immuni.2018.11.011
Year: 2019

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