Affinity Maturation of a Potent Family of HIV Antibodies Is Primarily Focused on Accommodating or Avoiding Glycans.

TitleAffinity Maturation of a Potent Family of HIV Antibodies Is Primarily Focused on Accommodating or Avoiding Glycans.
Publication TypeJournal Article
Year of Publication2015
AuthorsGarces F, Lee J H, de Val N, de la Peña ATorrents, Kong L, Puchades C, Hua Y, Stanfield RL, Burton DR, Moore JP, Sanders RW, Ward AB, Wilson IA
JournalImmunity
Volume43
Issue6
Pagination1053-63
Date Published12/15/2015
ISSN1097-4180
Abstract

The high-mannose patch on the HIV-1 envelope (Env) glycoprotein is the epicenter for binding of the potent broadly neutralizing PGT121 family of antibodies, but strategies for generating such antibodies by vaccination have not been defined. We generated structures of inferred antibody intermediates by X-ray crystallography and electron microscopy to elucidate the molecular events that occurred during evolution of this family. Binding analyses revealed that affinity maturation was primarily focused on avoiding, accommodating, or binding the N137 glycan. The overall antibody approach angle to Env was defined very early in the maturation process, yet some variation evolved in the PGT121 family branches that led to differences in glycan specificities in their respective epitopes. Furthermore, we determined a crystal structure of the recombinant BG505 SOSIP.664 HIV-1 trimer with a PGT121 family member at 3.0 Å that, in concert with these antibody intermediate structures, provides insights to advance design of HIV vaccine candidates.

DOI10.1016/j.immuni.2015.11.007
Alternate JournalImmunity
PubMed ID26682982
PubMed Central IDPMC4692269
Grant ListP01 AI110657 / AI / NIAID NIH HHS / United States
R37 AI036082 / AI / NIAID NIH HHS / United States
CHAVI-ID: 
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