Cell Reports
Volume 25, Issue 4, 23 October 2018, Pages 893-908.e7
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Article
Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth

https://doi.org/10.1016/j.celrep.2018.09.087Get rights and content
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Highlights

  • Computational strategy for prediction of infrequent HIV-1 Env glycan holes

  • Intact glycan shields at transmission are associated with neutralization breadth

  • Glycan holes fill in vivo to escape autologous neutralizing antibodies

  • Filling of glycan holes precedes development of neutralization breadth

Summary

Densely arranged N-linked glycans shield the HIV-1 envelope (Env) trimer from antibody recognition. Strain-specific breaches in this shield (glycan holes) can be targets of vaccine-induced neutralizing antibodies that lack breadth. To understand the interplay between glycan holes and neutralization breadth in HIV-1 infection, we developed a sequence- and structure-based approach to identify glycan holes for individual Env sequences that are shielded in most M-group viruses. Applying this approach to 12 longitudinally followed individuals, we found that transmitted viruses with more intact glycan shields correlated with development of greater neutralization breadth. Within 2 years, glycan acquisition filled most glycan holes present at transmission, indicating escape from hole-targeting neutralizing antibodies. Glycan hole filling generally preceded the time to first detectable breadth, although time intervals varied across hosts. Thus, completely glycan-shielded viruses were associated with accelerated neutralization breadth development, suggesting that Env immunogens with intact glycan shields may be preferred components of AIDS vaccines.

Keywords

neutralizing antibodies
glycan shield
HIV-1 envelope
transmitted founder
vaccine design

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These authors contributed equally

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