Virus-like Particles Identify an HIV V1V2 Apex-Binding Neutralizing Antibody that Lacks a Protruding Loop

Immunity
Evan M CaleJames M Binley

Abstract

Most HIV-1-specific neutralizing antibodies isolated to date exhibit unusual characteristics that complicate their elicitation. Neutralizing antibodies that target the V1V2 apex of the HIV-1 envelope (Env) trimer feature unusually long protruding loops, which enable them to penetrate the HIV-1 glycan shield. As antibodies with loops of requisite length are created through uncommon recombination events, an alternative mode of apex binding has been sought. Here, we isolated a lineage of Env apex-directed neutralizing antibodies, N90-VRC38.01-11, by using virus-like particles and conformationally stabilized Env trimers as B cell probes. A crystal structure of N90-VRC38.01 with a scaffolded V1V2 revealed a binding mode involving side-chain-to-side-chain interactions that reduced the distance the antibody loop must traverse the glycan shield, thereby facilitating V1V2 binding via a non-protruding loop. The N90-VRC38 lineage thus identifies a solution for V1V2-apex binding that provides a more conventional B cell pathway for vaccine design.

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Citations

Apr 14, 2018·Acta Crystallographica. Section D, Structural Biology·Paul Emsley, Max Crispin
Aug 9, 2017·Human Vaccines & Immunotherapeutics·Christopher A Cottrell, Andrew B Ward
Apr 30, 2019·Current Opinion in HIV and AIDS·Simone I Richardson, Penny L Moore
Apr 5, 2019·Current Opinion in HIV and AIDS·Andrew T McGuire
Aug 25, 2017·PloS One·Alexandre CalazansRoss Lindsay
Sep 7, 2018·Retrovirology·Elise Landais, Penny L Moore
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Oct 20, 2018·Nature Immunology·Devin Sok, Dennis R Burton
Oct 30, 2020·Viruses·Christophe CaillatWinfried Weissenhorn
Nov 6, 2021·Frontiers in Immunology·Sarah A Griffith, Laura E McCoy

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