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Immunity. 2017 Sep 19;47(3):524-537.e3. doi: 10.1016/j.immuni.2017.08.006. Epub 2017 Sep 12.

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

Author information

1
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
2
Genomics Research Center, Academia Sinica, Nankang, Taipei 115, Taiwan.
3
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
4
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, MA 02114, USA. Electronic address: burton@scripps.edu.

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.

KEYWORDS:

B cell affinity maturation; Env glycans; HIV envelope trimer; V2 apex epitope; bnAbs; broadly neutralizing antibodies; glycan engineering; virus escape

PMID:
28916265
PMCID:
PMC5613947
DOI:
10.1016/j.immuni.2017.08.006
[Indexed for MEDLINE]
Free PMC Article

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