|Title||Early Antibody Lineage Diversification and Independent Limb Maturation Lead to Broad HIV-1 Neutralization Targeting the Env High-Mannose Patch.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||MacLeod 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 Authors||IAVI Protocol C Investigators & The IAVI African HIV Research Network|
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.
|Grant List||R01 AI084817 / AI / NIAID NIH HHS / United States |
UM1 AI100663 / AI / NIAID NIH HHS / United States
Early Antibody Lineage Diversification and Independent Limb Maturation Lead to Broad HIV-1 Neutralization Targeting the Env High-Mannose Patch.