Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers

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

doi:10.1016/j.immuni.2018.11.011

Abstract

SummaryPassive 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.

Highlights

Several vaccine strategies are being pursued to stimulate protective immunity against HIV, including those that combine the elicitation of cellular and humoral responsesImmunity 50, 241–252, January 15, 2019 a 2018 The Author(s)
Immunized Macaques Were Grouped into High and low nAb titer (Low) neutralizing antibodies (nAbs)-Titer Animals Our goal was to assess the capability of vaccine-elicited tier 2 nAbs to protect from homologous tier 2 challenge with neutralization-resistant, pathogenic SHIVBG505 (Li et al, 2016)
We previously developed a protocol for the reliable induction of nAbs and immunized 78 non human primate (NHP) (Pauthner et al, 2017), inducing varying levels of autologous tier 2 nAb titers after three immunizations with native-like BG505 envelope glycoprotein (Env) trimers

Summary

Introduction

Several vaccine strategies are being pursued to stimulate protective immunity against HIV, including those that combine the elicitation of cellular and humoral responsesImmunity 50, 241–252, January 15, 2019 a 2018 The Author(s). Several vaccine strategies are being pursued to stimulate protective immunity against HIV, including those that combine the elicitation of cellular and humoral responses. One of the most intensively studied approaches is focused on inducing neutralizing antibodies (nAbs) to the virus. Pioneering monkey studies showed that DNA gp120-immunization induces nAb responses that can protect against tier 1 virus challenge (Barnett et al, 2008, 2010; Pal et al, 2006). Two recent studies investigated vaccine-induced protection from a mixed tier SIVsmE660 swarm and attribute protection, in part, to nAb and other Ab responses (Keele et al, 2017; Roederer et al, 2014). There is no clear evidence of vaccination-induced nAbs providing protection against viruses possessing hard-toneutralize clinically relevant tier 2 HIV Env in humans or non human primate (NHP) models

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