Controlled rapid synthesis and in vivo immunomodulatory effects of LM α(1,6)mannan with an amine linker.

The synthetic lipomannan (LM) α(1,6)mannans, already equipped with an amine linker on the reducing end, are rapidly synthesized in a size-, regio-, and stereocontrolled reaction. The size of the mannans is regulated through the concentration of the linker, applied during the controlled ring-opening polymerization reaction. The versatile amine linker enables a variety of glycan conjugations. The synthetic α(1,6)mannans exert adjuvant activities for a real vaccine antigen, tetanus toxoid (TT) in vitro, as demonstrated by the increased secretion of proinflammatory cytokines TNF-α and IL-6 from the treated macrophages. A conjugation of synthetic α(1,6)mannan with TT can also enhance immune response to TT in vivo after immunization as shown by an increase in TNF-α, IFN-γ, and IL-2 production in splenocytes.