Rapid and Focused Maturation of a VRC01-Class HIV Broadly Neutralizing Antibody Lineage Involves Both Binding and Accommodation of the N276-Glycan.

Authors: Umotoy, Jeffrey and Bagaya, Bernard S and Joyce, Collin and Schiffner, Torben and Menis, Sergey and Saye-Francisco, Karen L and Biddle, Trevor and Mohan, Sanjay and Vollbrecht, Thomas and Kalyuzhniy, Oleksander and Madzorera, Sharon and Kitchin, Dale and Lambson, Bronwen and Nonyane, Molati and Kilembe, William and Poignard, Pascal and Schief, William R and Burton, Dennis R and Murrell, Ben and Moore, Penny L and Briney, Bryan and Sok, Devin and Landais, Elise

The VH1-2 restricted VRC01-class of antibodies targeting the HIV envelope CD4 binding site are a major focus of HIV vaccine strategies. However, a detailed analysis of VRC01-class antibody development has been limited by the rare nature of these responses during natural infection and the lack of longitudinal sampling of such responses. To inform vaccine strategies, we mapped the development of a VRC01-class antibody lineage (PCIN63) in the subtype C infected IAVI Protocol C neutralizer PC063. PCIN63 monoclonal antibodies had the hallmark VRC01-class features and demonstrated neutralization breadth similar to the prototype VRC01 antibody, but were 2- to 3-fold less mutated. Maturation occurred rapidly within ~24 months of emergence of the lineage and somatic hypermutations accumulated at key contact residues. This longitudinal study of broadly neutralizing VRC01-class antibody lineage reveals early binding to the N276-glycan during affinity maturation, which may have implications for vaccine design.Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Journal: Immunity
DOI: 10.1016/j.immuni.2019.06.004
Year: 2019

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