Holes in the Glycan Shield of the Native HIV Envelope Are a Target of Trimer-Elicited Neutralizing Antibodies
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McCoy-2016-Holes in the Glycan.pdf
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Author(s) • • • • • • • • •
McCoy, Laura E.
van Gils, Marit J.
Ozorowski, Gabriel
Messmer, Terrence
Briney, Bryan
Voss, James E.
Kulp, Daniel W.
Macauley, Matthew S.
Sok, Devin
Pauthner, Matthias
Date Issued
August 2016
Journal
Cell Reports
Publisher
Elsevier
Citation
McCoy, Laura E. et al. “Holes in the Glycan Shield of the Native HIV Envelope Are a Target of Trimer-Elicited Neutralizing Antibodies.” Cell Reports 16.9 (2016): 2327–2338.
Version
Final published version
Abstract
A major advance in the search for an HIV vaccine has been the development of a near-native Envelope trimer (BG505 SOSIP.664) that can induce robust autologous Tier 2 neutralization. Here, potently neutralizing monoclonal antibodies (nAbs) from rabbits immunized with BG505 SOSIP.664 are shown to recognize an immunodominant region of gp120
centered on residue 241. Residue 241 occupies a hole in the glycan defenses of the BG505 isolate, with fewer than 3% of global isolates lacking a glycan site at this position. However, at least one conserved glycan site is missing in 89% of viruses, suggesting the presence of glycan holes in most
HIV isolates. Serum evidence is consistent with targeting of holes in natural infection. The immunogenic nature of breaches in the glycan shield has been under-appreciated in previous attempts to understand autologous neutralizing antibody responses and has important potential consequences for HIV vaccine design.
MIT Department
Ragon Institute of MGH, MIT and Harvard
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2016.07.074