Carbohydrates as putative pattern recognition receptor agonists in vaccine development.

It is essential to overcome the challenges of structural complexity, synthesis, source heterogeneity, and lack of analytical tools, to elucidate the molecular mechanisms of carbohydrate-based adjuvants for the design of new putative vaccines. The physicochemical factors of carbohydrates, including molecular weight, monosaccharide composition, functional groups, and spatial conformation, determine their recognition by pattern recognition receptors, consequently affecting their immunomodulatory activities. Carbohydrate-based adjuvants may harbor advantages in the regulation of antigen transport, presentation, and processing, thus enriching the type of adaptive immunity that can be initiated. Advanced chemical and computational technologies can provide new tools for the development of carbohydrate-based adjuvants. By increasing our efforts to elucidate the immunomodulatory mechanisms of carbohydrates, especially those representing or mimicking microbial infections, we might provide new biological evidence and engineering perspectives for the design of next-generation vaccine adjuvants. 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. [ABSTRACT FROM AUTHOR]