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HIV Envelope Glycoform Heterogeneity and Localized Diversity Govern the Initiation and Maturation of a V2 Apex Broadly Neutralizing Antibody Lineage

Landais, E
; 
Murrell, B
; 
Briney, B
; 
Murrell, S
; 
Rantalainen, K
; 
Berndsen, ZT
; 
Ramos, A
; 
Wickramasinghe, L
; 
Smith, ML
; 
Eren, K
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Post-print
Date
2017-11-21
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Subject
AIDS Vaccines
 Antibodies, Neutralizing
 Cell Lineage
 Complementarity Determining Regions
 HIV Antibodies
 Humans
 env Gene Products, Human Immunodeficiency Virus
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http://hdl.handle.net/20.500.12613/4849
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DOI
10.1016/j.immuni.2017.11.002
Abstract
© 2017 The Authors Understanding how broadly neutralizing antibodies (bnAbs) to HIV envelope (Env) develop during natural infection can help guide the rational design of an HIV vaccine. Here, we described a bnAb lineage targeting the Env V2 apex and the Ab-Env co-evolution that led to development of neutralization breadth. The lineage Abs bore an anionic heavy chain complementarity-determining region 3 (CDRH3) of 25 amino acids, among the shortest known for this class of Abs, and achieved breadth with only 10% nucleotide somatic hypermutation and no insertions or deletions. The data suggested a role for Env glycoform heterogeneity in the activation of the lineage germline B cell. Finally, we showed that localized diversity at key V2 epitope residues drove bnAb maturation toward breadth, mirroring the Env evolution pattern described for another donor who developed V2-apex targeting bnAbs. Overall, these findings suggest potential strategies for vaccine approaches based on germline-targeting and serial immunogen design. Understanding the molecular basis of HIV Env-specific broadly neutralizing antibodies (bnAbs) development is key for vaccine design. Landais et al. find that glycan heterogeneity played a role in the activation of V2 apex PCT64 bnAbs precursor and that viral evolution was similar to CAP256, another donor with V2 apex bnAbs.
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Elsevier BV
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Immunity
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