High-affinity anti-glycan antibodies: challenges and strategies

•High-affinity anti-glycan antibodies can now be produced by using synthetic immunogen and adjuvants that specifically help B cell maturation and increase somatic hypermutation.•Re-design of current glycan-based vaccines would help protect immunocompromised as well as elderly patients who do not respond to current commercial conjugate vaccines.•The same new approaches could be used to target unique glycans of cancer cells and numerous infectious microbes with surface-exposed glycans. High-affinity binding of antibodies provides for increased specificity and usually higher effector functions in vivo. This goal, well documented in cancer immunotherapy, is very relevant to vaccines as well, and has particularly significant application toward glycan antigens. The inability to elicit high-affinity antibodies has limited potential applications of glycan-based immunogens, giving rise to insufficient population coverage due to low titers and short duration of protection. That such vaccines have achieved widespread use in spite of these shortcomings highlights the surpassing importance of glycans as prophylactic immunological targets. New advances in the combination of synthetic chemistry, bioconjugation, and mechanistic immunology offer the possibility to vastly expand the number of potential molecular targets in cancer and infectious diseases by opening a wider world of carbohydrate structures to immunological recognition and high-affinity response.