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,
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.
- Downloaded 198 times
- Download rankings, all-time:
- Site-wide: 110,820
- In immunology: 3,190
- Year to date:
- Site-wide: 91,921
- Since beginning of last month:
- Site-wide: 121,302
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!