Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers
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Description
Published version
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2.5 MB
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Checksum (MD5)
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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
Date Issued
January 2019
Journal
Immunity
Publisher
Elsevier BV
Citation
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
Version
Final published version
Abstract
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.
MIT Department
Ragon 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
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1016/J.IMMUNI.2018.11.011
