HIV Envelope Glycoform Heterogeneity and Localized Diversity Govern the Initiation and Maturation of a V2 Apex Broadly Neutralizing Antibody Lineage
Genre
Post-printDate
2017-11-21Author
Landais, EMurrell, B
Briney, B
Murrell, S
Rantalainen, K
Berndsen, ZT
Ramos, A
Wickramasinghe, L
Smith, ML
Eren, K
de Val, N
Wu, M
Cappelletti, A
Umotoy, J
Lie, Y
Wrin, T
Algate, P
Chan-Hui, PY
Karita, E
Ward, AB
Wilson, IA
Burton, DR
Smith, D
Pond, SLK
Poignard, P
Subject
AIDS VaccinesAntibodies, 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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10.1016/j.immuni.2017.11.002Abstract
© 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.Citation to related work
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http://dx.doi.org/10.34944/dspace/4831