A Broadly Neutralizing Macaque Monoclonal Antibody Against the HIV-1 V3-Glycan Patch
Christopher O. Barnes,
Julio C. C. Lorenzi,
Christian T. Mayer,
Thiago Y. Oliveira,
Kristie M Gordon,
Harry B. Gristick,
Anthony P. West,
Michael S. Seaman,
Malcolm A Martin,
Pamela J Bjorkman,
Michel C. Nussenzweig
Posted 10 Aug 2020
bioRxiv DOI: 10.1101/2020.08.10.244582
Posted 10 Aug 2020
A small fraction of HIV-1 infected humans develop potent broadly neutralizing antibodies (bNAbs) against HIV-1 that can protect macaques from infection with simian immunodeficiency HIV chimeric virus (SHIV). Similarly, a small number of macaques infected with SHIVs also develop broadly neutralizing serologic activity, but less is known about the nature of these simian antibodies. Here we report on a monoclonal antibody, Ab1485, isolated from a macaque infected with SHIVAD8 that developed broadly neutralizing serologic activity mapping to the V3-glycan region of HIV-1 Env. Ab1485 neutralizes 38.1 % of HIV-1 isolates in a panel of 42 pseudoviruses with a geometric mean IC50 of 0.055 μg/ml and SHIVAD8 with an IC50 of 0.028 μg/ml. Ab1485 binds to the V3-glycan epitope in a glycan-dependent manner as determined by ELISA and neutralization assays with JRCSF mutant viruses. 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. Finally, intravenous infusion of Ab1485 protected macaques from a high dose intrarectal challenge with SHIVAD8. We conclude that macaques can develop bNAbs against the V3-glycan patch that resemble human V3-glycan bNAbs. ### Competing Interest Statement The authors have declared no competing interest.
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