PT  - JOURNAL ARTICLE
AU  - Gemma E. Seabright
AU  - Christopher A. Cottrell
AU  - Marit J. van Gils
AU  - Alessio D’addabbo
AU  - David J. Harvey
AU  - Anna-Janina Behrens
AU  - Joel D. Allen
AU  - Yasunori Watanabe
AU  - Allison Maker
AU  - Snezana Vasiljevic
AU  - Natalia de Val
AU  - Rogier W. Sanders
AU  - Andrew B. Ward
AU  - Max Crispin
TI  - Networks of HIV-1 envelope glycans maintain antibody epitopes in the face of glycan additions and deletions
AID  - 10.1101/2020.02.21.959981
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.02.21.959981
4099  - http://biorxiv.org/content/early/2020/02/23/2020.02.21.959981.short
4100  - http://biorxiv.org/content/early/2020/02/23/2020.02.21.959981.full
AB  - Numerous broadly neutralizing antibodies (bnAbs) have been identified that target the glycans of the HIV-1 envelope spike. Neutralization breadth is notable given that glycan processing can be substantially influenced by the presence or absence of neighboring glycans. Here, using a stabilized recombinant envelope trimer, we investigate the degree to which mutations in the glycan network surrounding an epitope impact the fine glycan processing of antibody targets. Using cryo-electron microscopy and site-specific glycan analysis, we reveal the hierarchy of importance of glycans in the formation of the 2G12 bnAb epitope, and show that the epitope is only subtly impacted by variations in the glycan network. In contrast, we show that the PG9 and PG16 glycan-based epitopes at the trimer apex are dependent on the presence of the highly conserved surrounding glycans. Glycan networks underpin the conservation of bnAb epitopes and are an important parameter in immunogen design.