Abstract

The induction of broad and potent immunity by vaccines is the key focus of research efforts aimed at protecting against HIV-1 infection. Soluble native-like HIV-1 envelope glycoproteins have shown promise as vaccine candidates as they can induce potent autologous neutralizing responses in rabbits and non-human primates. In this study, monoclonal antibodies were isolated and characterized from rhesus macaques immunized with the BG505 SOSIP.664 trimer to better understand vaccine-induced antibody responses. Our studies reveal a diverse landscape of antibodies recognizing immunodominant strain-specific epitopes and non-neutralizing neo-epitopes. Additionally, we isolated a subset of mAbs against an epitope cluster at the gp120-gp41 interface that recognize the highly conserved fusion peptide and the glycan at position 88 and have characteristics akin to several human-derived broadly neutralizing antibodies.

Highlights

  • HIV-1 continues to cause significant morbidity and mortality around the world with an estimated 1.7 million new infections in 2018 [1], which emphasizes the need for an effective prophylactic vaccine

  • Major efforts are currently directed towards developing vaccine strategies to successfully elicit broadly neutralizing antibodies against HIV-1

  • envelope glycoprotein (Env) trimer was studied through the isolation of monoclonal antibodies in rhesus macaques (RMs) after immunization

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Summary

Introduction

HIV-1 continues to cause significant morbidity and mortality around the world with an estimated 1.7 million new infections in 2018 [1], which emphasizes the need for an effective prophylactic vaccine. Studies of infected patients have led to the isolation of NAbs against multiple different epitopes on the Env surface that are capable of both neutralizing most circulating strains and providing passive protection against repeated viral challenges in non-human primates (NHPs) [2,3,4,5]. Extensive research efforts, including structure-based engineering of Env immunogens, are currently directed towards developing vaccine strategies to successfully elicit broadly neutralizing antibodies (bNAbs) against specific Env epitopes [6,7,8,9,10,11,12]. NAbs induced by SOSIP trimers in NHPs can protect against challenge with an autologous Simian-Human Immunodeficiency virus (SHIV) [17,18]. As NAbs with the required breadth of activity have not yet been induced in trimer-immunized animals, improvements to current vaccine design and delivery strategies are clearly needed

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