Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth.
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.
Wagh, K; Kreider, EF; Li, Y; Barbian, HJ; Learn, GH; Giorgi, E; Hraber, PT; Decker, TG; Smith, AG; Gondim, MV; Gillis, L; Wandzilak, J; Chuang, G-Y; Rawi, R; Cai, F; Pellegrino, P; Williams, I; Overbaugh, J; Gao, F; Kwong, PD; Haynes, BF; Shaw, GM; Borrow, P; Seaman, MS; Hahn, BH; Korber, B
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