Carbohydrates as putative pattern recognition receptor agonists in vaccine development

Adjuvants are essential components of modern vaccines. One general mechanism underlying their immunostimulatory functions is the activation of pattern recognition receptors (PRRs) of innate immune cells. Carbohydrates – as essential signaling molecules on microbial surfaces – are potent PRR agonists and candidate materials for adjuvant design. Here, we summarize the latest trends in developing carbohydrate-containing adjuvants, with fresh opinions on how the physicochemical characteristics of the glycans (e.g., molecular size, assembly status, monosaccharide components, and functional group patterns) affect their adjuvant activities in aiding antigen transport, regulating antigen processing, and enhancing adaptive immune responses. From a translational perspective, we also discuss potential technologies for solving long-lasting challenges in carbohydrate adjuvant design.