Facile Preparation of Carbohydrate-Containing Adjuvants Based on Self-Assembling Glycopeptide Conjugates

Carbohydrates are intriguing biomolecules possessing diverse biological activities, including immune stimulating capability. However, their biomedical applications have been limited by their complex and heterogeneous structures. In this study, we have utilized a self-assembling glycopeptide conjugate (GPC) system to produce uniform nanoribbons appending homogeneous oligosaccharides with multivalency. This system successfully translates the nontrivial structural differences of oligomannoses into varied binding affinities to C-type lectin receptors (CLRs). We have shown that GPCs could promote the CLR-mediated endocytosis of ovalbumin (OVA) antigen, and two mannotriose-modified peptides F3m2 and F3m5 exhibit potent activity in inducing antigen-presenting cell maturation, as indicated by increased CD86 and MHCII expression. In vivo studies demonstrated that GPCs, combined with OVA antigen, significantly enhanced OVA-specific antibody production. Specifically, F3m2 and F3m5 exhibited the highest immunostimulatory effects, eliciting both Th1- and Th2-biased immune responses and promoting differentiation of CD4⁺ and CD8⁺  T cells. These findings highlight the potential of GPCs as vaccine adjuvants, and showcase their versatility in exploiting the biological functions of carbohydrates.