Targeting Glycans of HIV Envelope Glycoproteins for Vaccine Design

The surface of the envelope spike of the human immunodeficiency virus (HIV) is covered with a dense array of glycans, which is sufficient to impede the host antibody response while maintaining a window for receptor recognition. The glycan density significantly exceeds that typically observed on self glycoproteins and is sufficiently high to disrupt the maturation process of glycans, from oligomannose- to complex-type glycosylation, that normally occurs during glycoprotein transit through the secretory system. It is notable that this generates a degree of homogeneity not seen in the highly mutated protein moiety. The conserved, close glycan packing and divergences from default glycan processing give a window for immune recognition. Encouragingly, in a subset of individuals, broadly neutralizing antibodies (bNAbs) have been isolated that recognize these features and are protective in passive-transfer models. Here, we review the recent advances in our understanding of the glycan shield of HIV and outline the strategies that are being pursued to elicit glycan-binding bNAbs by vaccination.