Mapping the immunogenic landscape of near-native HIV-1 envelope trimers in non-human primates

• DOI: 10.1371/journal.ppat.1008753
• Publication Date: 2020-08-31T20:04:20Z
• Authors: Christopher A. Co...; Jelle van Schooten; Charles A. Bowman; Meng Yuan; David Oyen; Mia Shin; Robert Morpurgo; Patricia van der ...; Mariëlle van Breemen; Jonathan L. Torres; Raj Patel; Justin Gross; Leigh M. Sewall; Jeffrey Copps; Gabriel Ozorowski; Bartek Nogal; Devin Sok; Eva G. Rakasz; Celia Labranche; Vladimir Vigdorovich; Scott Christley; Diane G. Carnathan; D. Noah Sather; David Montefiori; Guido Silvestri; Dennis R. Burton; John P. Moore; Ian A. Wilson; Rogier W. Sanders; Andrew B. Ward; Marit J. van Gils
• Keywords: AIDS Vaccines; 0301 basic medicine; 0303 health sciences; QH301-705.5; RC581-607; HIV Antibodies; HIV Envelope Protein gp120; Macaca mulatta; HIV Envelope Protein gp41; 3. Good health; Antibodies, Monoclonal, Murine-Derived; Epitopes; 03 medical and health sciences; HIV-1; Animals; Immunologic diseases. Allergy; Biology (General); Protein Multimerization; Epitope Mapping; Research Article

AbstractThe 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.