Synthesis of sulfated lactosyl glycosides for evaluation in vaccine adjuvant formulations†

Adjuvants are essential components of vaccines as they enable protection against multiple pathogens by enhancing the duration, magnitude and or quality of immune responses. SLA Archaeosomes, a type of liposome composed of sulfated lactosyl archaeol (SLA) glycolipids, are highly stable vaccine adjuvants that have been shown to induce strong immune responses in preclinical models of infectious disease and cancer. To better understand the mechanism of activity behind SLA archaeosomes strong immunogenic properties, we studied the effect of structural change on vaccine adjuvanticity. Herein, we report the synthesis of three new sulfated lactosyl glycosides (SLGs) by replacing the archaeol moiety with various side-chains. These derivatives were characterized using nuclear magnetic resonance, mass spectrometry, and thin layer chromatography for identity and purity assessment. The SLGs were co-assembled in the presence of DMPC and cholesterol to produce lipid vesicles. The abilities of the SLG-based liposomes to act as vaccine adjuvants were compared to SLA archaeosomes in an in vivo murine vaccine model.