Vaccine-induced protection from homologous Tier 2 simian-human immunodeficiency virus challenge in nonhuman primates
Joseph P Nkolola,
Samantha M Reiss,
Benjamin von Bredow,
Cristopher A. Cottrell,
Daniel W Kulp,
Jeong Hyun Lee,
Salvatore T Butera,
David T Evans,
Ian A. Wilson,
Rich T. Wyatt,
Darrell J Irvine,
William R Schief,
Andrew B. Ward,
Rogier W Sanders,
George M Shaw,
Dan H Barouch,
Dennis R. Burton
Posted 29 Oct 2018
bioRxiv DOI: 10.1101/454769 (published DOI: 10.1016/j.immuni.2018.11.011)
Posted 29 Oct 2018
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 following 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 from the BG505 HIV isolate. Repeat intrarectal challenge with homologous Tier 2 SHIVBG505 led to rapid infection in unimmunized and low-titer animals. In contrast, high-titer animals demonstrated protection that was gradually lost as nAb titers waned over weeks to months. From these results, we determined that an autologous serum ID50 nAb titer of ~1:500 was required to afford over 90% protection from medium-dose SHIV infection. We further identified autologous nAb titers, but not ADCC or T cell activity, as strong correlates of protection. These results provide proof-of-concept that 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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