Synthesis, Liposomal Formulation, and Immunological Evaluation of a Minimalistic Carbohydrate-α-GalCer Vaccine Candidate

Fully
synthetic glycan-based vaccines hold great potential as preventive
and therapeutic vaccines against infectious diseases as well as cancer.
Here, we present a two-component platform based on the facile conjugation
of carbohydrate antigens to α-galactosylceramide (α-GalCer)
to yield fully synthetic vaccine candidates. Formulation of the cancer-associated
Tn antigen glycolipid model vaccine candidate into liposomes of different
sizes and subsequent immunization of mice generated specific, high-affinity
antibodies against the carbohydrate antigen with characteristics of
T cell-dependent immunity. Liposome formulation elicited more reproducible
glycan immunity than a conventional glycoconjugate vaccine bearing
the same glycan antigen did. Further evaluation of the immune response
revealed that the size of the liposomes influenced the glycan antibody
responses toward either a cellular (Th1) or a humoral (Th2) immune
phenotype. The glycolipid vaccine platform affords strong and robust
antiglycan antibody responses in vivo without the
need for an external adjuvant.