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Immunity
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Immunity
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Article . 2018 . Peer-reviewed
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Immunity
Article . 2019
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Rapid and Focused Maturation of a VRC01-Class Broadly Neutralizing Antibody Lineage Involves Both Binding and Accommodation of the N276-Glycan

Authors: Umotoy, Jeffrey; Bagaya, Bernard S.; Joyce, Collin; Schiffner, Torben; Menis, Sergey; Saye-Francisco, Karen L.; Biddle, Trevor; +16 Authors

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

Abstract

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.

Keywords

AIDS Vaccines, B-Lymphocytes, Antibody Affinity, Antibodies, Monoclonal, HIV Infections, HIV Antibodies, HIV Envelope Protein gp120, Antibodies, Neutralizing, Complementarity Determining Regions, Article, Polysaccharides, CD4 Antigens, HIV-1, Humans, Amino Acid Sequence, Broadly Neutralizing Antibodies, Protein Binding

  • BIP!
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    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    73
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 1%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
73
Top 1%
Top 10%
Top 1%
Green
hybrid