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

Publication date: Available online 12 September 2017
Source:Immunity
Author(s): Raiees Andrabi, Ching-Yao Su, Chi-Hui Liang, Sachin S. Shivatare, Bryan Briney, James E. Voss, Salar Khan Nawazi, Chung-Yi Wu, Chi-Huey Wong, Dennis R. Burton
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.

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Teaser

Understanding the molecular basis for the development of HIV Env-specific bnAbs is key for vaccine design. Andrabi et al. find that CAP256 V2 apex lineage Abs affinity mature with sialic acid containing complex-type glycans on HIV envelope trimer. This glycan recognition enables the development into bnAbs by resisting virus escape.


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