1. A broadly neutralizing macaque monoclonal antibody against the HIV-1 V3-Glycan patch
- Author
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Zijun Wang, Christopher O Barnes, Rajeev Gautam, Julio C Cetrulo Lorenzi, Christian T Mayer, Thiago Y Oliveira, Victor Ramos, Melissa Cipolla, Kristie M Gordon, Harry B Gristick, Anthony P West, Yoshiaki Nishimura, Henna Raina, Michael S Seaman, Anna Gazumyan, Malcolm Martin, Pamela J Bjorkman, Michel C Nussenzweig, and Amelia Escolano
- Subjects
anti hiv-1 ,broadly neutralizing ,antibody ,rhesus macaque ,v3 glycan ,patch antibody ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
A small fraction of HIV-1- infected humans develop broadly neutralizing antibodies (bNAbs) against HIV-1 that protect macaques from simian immunodeficiency HIV chimeric virus (SHIV). Similarly, a small number of macaques infected with SHIVs develop broadly neutralizing serologic activity, but less is known about the nature of simian antibodies. Here, we report on a monoclonal antibody, Ab1485, isolated from a macaque infected with SHIVAD8 that developed broadly neutralizing serologic activity targeting the V3-glycan region of HIV-1 Env. Ab1485 neutralizes 38.1% of HIV-1 isolates in a 42-pseudovirus panel with a geometric mean IC50 of 0.055 µg/mLl and SHIVAD8 with an IC50 of 0.028 µg/mLl. Ab1485 binds the V3-glycan epitope in a glycan-dependent manner. A 3.5 Å cryo-electron microscopy structure of Ab1485 in complex with a native-like SOSIP Env trimer showed conserved contacts with the N332gp120 glycan and gp120 GDIR peptide motif, but in a distinct Env-binding orientation relative to human V3/N332gp120 glycan-targeting bNAbs. Intravenous infusion of Ab1485 protected macaques from a high dose challenge with SHIVAD8. We conclude that macaques can develop bNAbs against the V3-glycan patch that resemble human V3-glycan bNAbs.
- Published
- 2020
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