How glycans of HIV Envelope spikes modulate interactions with broadly neutralizing antibodies

The Veesler lab at University of Washington published a study in eLife describing how N-linked glycans of HIV Envelope spikes interact with a broadly neutralizing antibody.

Using a combination of cryo electron microscopy and mass spectrometry, it was shown that glycans in and around the CD4 receptor binding site modulate interactions with the germline precursor to a class of broadly neutralizing antibodies. It was demonstrated that the VRC01 germline precursor can accommodate glycans in the epitope, even though it binds stronger when the glycans are shorter or completely absent.

The findings have important implications for HIV vaccine design. With the right choice of expression platform, immunogens can be produced with carefully tuned N-linked glycosylation in and around the CD4 receptor binding site. The aim is to find a perfect balance between the strength of interaction with VRC01 antibodies and the ability to accommodate glycans that are present in the Envelope spikes of the virus.