Effect of Chiral Purity on Adjuvanticity of Archaeol-Based Glycolipids

Archaeosomes composed
of sulfated lactosyl archaeol (SLA) glycolipids
from stereoisomerically pure archaeol (1) are vaccine
adjuvants that can boost immunogenicity and vaccine efficacy in preclinical
models. Herein, we report a new synthesis of 2,3-bis­((3,7,11,15-tetramethylhexadecyl)­oxy)
propan-1-ol (3) by treating (±)-3-benzyloxy-1,2-propanediol
with a mesylated phytol derivative through a double nucleophilic substitution
reaction, followed by reductive debenzylation. Three SLA archaeosomes
from archaeols of different chiral purities were prepared, and the
effect of stereochemistry on their adjuvanticity toward ovalbumin
was investigated. It was found that all SLA archaeosomes induced strong
humoral and cell-mediated antigen-specific immune responses following
immunization of C57BL/6NCrl mice, with no significant differences,
irrespective of the chiral purities. The responses were comparable
or better than those obtained using mimetics of approved adjuvants.
The performance of SLA archaeosomes during immunization and their
lack of dependence on the stereochemistry of archaeol points toward
a promising, safe, scalable, and economically viable vaccine adjuvant
system.