Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers
Author(s)Pauthner, Matthias G.; Nkolola, Joseph P.; Havenar-Daughton, Colin; Murrell, Ben; Reiss, Samantha M.; Bastidas, Raiza; Prévost, Jérémie; Nedellec, Rebecca; Bredow, Benjamin von; Abbink, Peter; Cottrell, Christopher A.; Kulp, Daniel W. K; Tokatlian, Talar; Nogal, Bartek; Bianchi, Matteo; Li, Hui; Lee, Jeong Hyun; Butera, Salvatore T.; Evans, David T.; Hangartner, Lars; Finzi, Andrés; Wilson, Ian A.; Wyatt, Richard T.; Irvine, Darrell J.; Irvine, Darrell J; Schief, William R.; Ward, Andrew B.; Sanders, Rogier W.; Crotty, Shane; Shaw, George M.; Barouch, Dan H.; Burton, Dennis R.; ... Show more Show less
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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 SHIV BG505 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 ID 50 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.
DepartmentRagon Institute of MGH, MIT and Harvard; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Materials Science and Engineering; Koch Institute for Integrative Cancer Research at MIT
Pauthner, Matthias G., Joseph P. Nkolola, Colin Havenar-Daughton et al. "Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers." Immunity 50,1 (15 January 2019):p.241-252.eb © 2018 The Author(s). https://doi.org/10.1016/j.immuni.2018.11.011
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