Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth.
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.
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.