Conformationally Restricted Analogues of α-Galactosylceramide as Adjuvant in COVID-19 Subunit Vaccine

iNKT cells are a type of T lymphocyte that recognizes glycolipid antigens presented by CD1d protein. alpha GC is an agonistic glycolipid that activates iNKT cells and triggers immune modulatory cytokine responses, making it a promising vaccine adjuvant. To find more potent immunostimulating glycolipids, we prepared 4,6-O-galactosyl conformationally restricted analogues of alpha GC. Mice vaccinated with the SARS-CoV-2 RBD-Fc vaccine adjuvanted with these newly developed glycolipids produced robust anti-RBD antibody responses, comparable to those achieved with alpha GC. Importantly, we also found that omitting alpha GC, alpha-C-GalCer (Th1-type agonist), or C20:2 (Th2-type agonist) from the booster vaccine had negligible impact on antibody and cellular responses, potentially reducing the frequency of adjuvant use required to maintain potent immune responses.