Synthesis and Immunological Activity of Novel Oligo(ethylene glycol) Analogues of α‑Galactosylceramide

CD1d-arbitrated activation of i-NKT cells by α-galactosylceramide results in the effective secretion of Th1 and Th2 cytokines, with adjuvanticity skewed toward Th2 immunity. However, the polarization of immune response could be achieved by suitable modification of the glycolipid structure. In the current study, novel glycolipids with an amphiphilic oligo ethylene glycol lipid moiety bearing the benzyloxy group at the terminus on the acyl arm of sphingosine, exhibited CD1d ligand binding as quantified by IL-2 cytokine production. When immunized with quadrivalent split influenza virus in BALB/c mice, the novel ceramide analogues with a longer oligo (ethylene glycol) chain length induced significant levels of antibody (IgG) with Th1-polarized immune response.