Rxivist logo

HIV Envelope Trimer-Elicited Autologous Neutralizing Antibodies Bind a Region Overlapping the N332 Glycan Supersite

By Bartek Nogal, Laura E McCoy, Marit van Gils, Cristopher A. Cottrell, James E. Voss, Raiees Andrabi, Matthias Pauthner, Chi-Hui Liang, Terrence Messmer, Rebecca Nedellec, Mia Shin, Hannah L Turner, Gabriel Ozorowski, Rogier W Sanders, Dennis R. Burton, Andrew Ward

Posted 05 Nov 2019
bioRxiv DOI: 10.1101/831008 (published DOI: 10.1126/sciadv.aba0512)

To date, immunization studies of rabbits with the BG505 SOSIP.664 HIV envelope glycoprotein trimers have revealed the 241/289 glycan hole as the dominant neutralizing antibody epitope. Here, we isolated monoclonal antibodies from a rabbit that did not exhibit glycan hole-dependent autologous serum neutralization. The antibodies did not compete with a previously isolated glycan hole-specific antibody but did compete with N332 glycan supersite broadly neutralizing antibodies. A high resolution cryoEM structure of one of the antibodies in complex with the BG505 SOSIP.664 trimer demonstrated that, while the epitope recognized overlapped with the N332 glycan supersite by contacting the GDIR motif at the base of V3, the primary contacts were located in the variable V1 loop. These data suggest that strain-specific responses to V1 may interfere with broadly neutralizing responses to the N332 glycan supersite and vaccine immunogens may require engineering to minimize these off-target responses or steer them toward a more desirable pathway.

Download data

  • Downloaded 312 times
  • Download rankings, all-time:
    • Site-wide: 94,023
    • In immunology: 2,766
  • Year to date:
    • Site-wide: 134,786
  • Since beginning of last month:
    • Site-wide: 131,743

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide