Identification of Mannose-Capped-Arabinomannan 101-mer as a Potential Influenza Virus Vaccine Adjuvant

Many natural bacterial components as adjuvants can activate the host immune system, but the excessive toxicity and structure-identification challenge limit their applications and structure-activity relationship studies. Herein, we report the role of a series of chemically synthesized mannose-capped arabinomannan motifs from Mycobacterium tuberculosis cell wall, including 18-mer, 19-mer, 27-mer, and 101-mer in regulating host immunity. As an influenza vaccine adjuvant, 101-mer induced significantly enhanced anti-influenza antibody response and immune protection compared with other arabinomannan motifs. 101-mer elicited robust immunoenhancement while exhibiting a favorable tolerability profile, as it did not trigger any observable physiological toxicity or inflammatory reactions in various organs. Mechanistically, we found 101-mer may serve as a Dectin-2 agonist to activate host immunity through Syk/NF-κB signaling. This study provided a new oligosaccharide candidate that can satisfy the required "efficacy-safety" balance for clinical adjuvant development.