Glycosylation as a tool for rational vaccine design

The discovery of broadly neutralizing antibodies that can neutralize multiple strains or subtypes of a pathogen has renewed interest in the development of broadly protective vaccines. To that end, there has been an interest in designing immunofocusing strategies to direct the immune response to specific, conserved regions on antigenic proteins. Modulation of glycosylation is one such immunofocusing strategy; extensive glycosylation is often exploited by pathogens for immune evasion. Masking epitopes on protein immunogens with “self” glycans can also shield the underlying protein surface from humoral immune surveillance. We review recent advances in applying glycosylation as an immunofocusing tool. We also highlight recent interesting work in the HIV‐1 field involving the identification and elicitation of broadly neutralizing antibodies that incorporate glycans into their binding epitopes. The elicitation of broadly neutralizing antibodies is the goal of many vaccines. Immunofocusing strategies aim to redirect the immune response to conserved epitopes on antigenic proteins. Many pathogens evade immune surveillance by exploiting host‐cell machinery to glycosylate protein surfaces; the addition of glycosylation can similarly be used in vaccine design to shield selected regions of the protein surface from the immune system. Here, we review recent advances in utilizing glycosylation as an immunofocusing tool.