Glycans Function as Anchors for Antibodies and Help Drive HIV Broadly Neutralizing Antibody Development.

TitleGlycans Function as Anchors for Antibodies and Help Drive HIV Broadly Neutralizing Antibody Development.
Publication TypeJournal Article
Year of Publication2017
AuthorsAndrabi R, Su C-Y, Liang C-H, Shivatare SS, Briney B, Voss JE, Nawazi SKhan, Wu C-Y, Wong C-H, Burton DR
JournalImmunity
Volume47
Issue3
Pagination524-537
Date Published09/19/2017
ISSN1097-4180
Abstract

Apex broadly neutralizing HIV antibodies (bnAbs) recognize glycans and protein surface close to the 3-fold axis of the envelope (Env) trimer and are among the most potent and broad Abs described. The evolution of apex bnAbs from one donor (CAP256) has been studied in detail and many Abs at different stages of maturation have been described. Using diverse engineering tools, we investigated the involvement of glycan recognition in the development of the CAP256.VRC26 Ab lineage. We found that sialic acid-bearing glycans were recognized by germline-encoded and somatically mutated residues on the Ab heavy chain. This recognition provided an "anchor" for the Abs as the core protein epitope varies, prevented complete neutralization escape, and eventually led to broadening of the response. These findings illustrate how glycan-specific maturation enables a human Ab to cope with pathogen escape mechanisms and will aid in optimization of immunization strategies to induce V2 apex bnAb responses.

DOI10.1016/j.immuni.2017.08.006
Alternate JournalImmunity
PubMed ID28916265
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