Early Antibody Lineage Diversification and Independent Limb Maturation Lead to Broad HIV-1 Neutralization Targeting the Env High-Mannose Patch.

TitleEarly Antibody Lineage Diversification and Independent Limb Maturation Lead to Broad HIV-1 Neutralization Targeting the Env High-Mannose Patch.
Publication TypeJournal Article
Year of Publication2016
AuthorsMacLeod DT, Choi NM, Briney B, Garces F, Ver LS, Landais E, Murrell B, Wrin T, Kilembe W, Liang C-H, Ramos A, Bian CB, Wickramasinghe L, Kong L, Eren K, Wu C-Y, Wong C-H, Pond SLKosakovs, Wilson IA, Burton DR, Poignard P
Corporate AuthorsIAVI Protocol C Investigators & The IAVI African HIV Research Network
JournalImmunity
Volume44
Issue5
Pagination1215-26
Date Published05/17/2016
ISSN1097-4180
Abstract

The high-mannose patch on HIV Env is a preferred target for broadly neutralizing antibodies (bnAbs), but to date, no vaccination regimen has elicited bnAbs against this region. Here, we present the development of a bnAb lineage targeting the high-mannose patch in an HIV-1 subtype-C-infected donor from sub-Saharan Africa. The Abs first acquired autologous neutralization, then gradually matured to achieve breadth. One Ab neutralized >47% of HIV-1 strains with only ∼11% somatic hypermutation and no insertions or deletions. By sequencing autologous env, we determined key residues that triggered the lineage and participated in Ab-Env coevolution. Next-generation sequencing of the Ab repertoire showed an early expansive diversification of the lineage followed by independent maturation of individual limbs, several of them developing notable breadth and potency. Overall, the findings are encouraging from a vaccine standpoint and suggest immunization strategies mimicking the evolution of the entire high-mannose patch and promoting maturation of multiple diverse Ab pathways.

DOI10.1016/j.immuni.2016.04.016
Alternate JournalImmunity
PubMed ID27192579
Grant ListR01 AI084817 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
CHAVI-ID: 
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