@article{c559d007008044e09963083496114b37,
title = "The Glycan Hole Area of HIV-1 Envelope Trimers Contributes Prominently to the Induction of Autologous Neutralization",
abstract = "The human immunodeficiency virus type 1 (HIV-1) trimeric envelope glycoprotein (Env) is heavily glycosylated, creating a dense glycan shield that protects the underlying peptidic surface from antibody recognition. The absence of conserved glycans, due to missing potential N-linked glycosylation sites (PNGS), can result in strain-specific, autologous neutralizing antibody (NAb) responses. Here, we sought to gain a deeper understanding of the autologous neutralization by introducing holes in the otherwise dense glycan shields of the AMC011 and AMC016 SOSIP trimers. Specifically, when we knocked out the N130 and N289 glycans, which are absent from the well-characterized B41 SOSIP trimer, we observed stronger autologous NAb responses. We also analyzed the highly variable NAb responses induced in rabbits by diverse SOSIP trimers from subtypes A, B, and C. Statistical analysis, using linear regression, revealed that the cumulative area exposed on a trimer by glycan holes correlates with the magnitude of the autologous NAb response.",
keywords = "Autologous neutralization, Env trimer, Glycan shield, HIV-1, Immunization, SOSIP, Vaccine",
author = "Anna Schorcht and Cottrell, {Christopher A.} and Pavel Pugach and Ringe, {Rajesh P.} and Han, {Alvin X.} and Allen, {Joel D.} and {van den Kerkhof}, {Tom L. G. M.} and Seabright, {Gemma E.} and Schermer, {Edith E.} and Ketas, {Thomas J.} and Burger, {Judith A.} and {van Schooten}, Jelle and LaBranche, {Celia C.} and Gabriel Ozorowski and {de Val}, Natalia and Bader, {Daniel L. V.} and Hanneke Schuitemaker and Russell, {Colin A.} and Montefiori, {David C.} and {van Gils}, {Marit J.} and Max Crispin and Klasse, {P. J.} and Ward, {Andrew B.} and Moore, {John P.} and Sanders, {Rogier W.}",
note = "Funding Information: The Amsterdam Cohort Studies on HIV Infection and AIDS, a collaboration between the Amsterdam Health Service, the Academic Medical Center of the University of Amsterdam, Sanquin Blood Supply Foundation, Medical Center Jan van Goyen, and the HIV Focus Center of the DC-Clinics, are part of the Netherlands HIV Monitoring Foundation and financially supported by the Center for Infectious Disease Control of the Netherlands National Institute for Public Health and Environment. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Publisher Copyright: {\textcopyright} 2022 Schorcht et al.",
year = "2022",
month = jan,
day = "1",
doi = "https://doi.org/10.1128/JVI.01552-21",
language = "English",
volume = "96",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "1",
}