Rapid and Focused Maturation of a VRC01-Class Broadly Neutralizing Antibody Lineage Involves Both Binding and Accommodation of the N276-Glycan
Rapid and Focused Maturation of a VRC01-Class Broadly Neutralizing Antibody Lineage Involves Both Binding and Accommodation of the N276-Glycan
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.
- University of KwaZulu-Natal South Africa
- National Health Laboratory Service South Africa
- UNIVERSITE GRENOBLE ALPES France
- Institut de Recherche Interdisciplinaire de Grenoble France
- UNIVERSITY OF CALIFORNIA, SAN DIEGO
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
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
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