Figure 1.

Glycopeptide mimics of HIV epitopes and the glycan trimming hypothesis. (a) The high-mannose patch (HMP) on HIV’s gp120 protein is a target of broadly neutralizing antibodies (bnAbs), and glycopeptides that mimic the HMP are attractive vaccine candidates. (b) Our method for in vitro selection of glycopeptides that mimic the HMP. (c) Antibodies elicited by glycopeptide HMP mimics have so far preferentially targeted the glycan core rather than the Manα1→2Man “tips” targeted by many bnAbs. (d) Immunization kinetics may influence glycan microspecificity: in bolus immunization, serum mannosidase trimming likely truncates most glycans before the bulk of affinity maturation; we hypothesize that, by contrast, continuous or repetitive immunization will provide fresh intact Man₉ glycan, against which Manα1→2Man-specific antibodies could develop in germinal centers that were originally established by intact Man₉ earlier in the immunization.