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

ABSTRACT 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.