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

J Med Chem. 2018 Jun 14;61(11):4918-4927. doi: 10.1021/acs.jmedchem.8b00312. Epub 2018 May 18.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Tumor-Associated, Carbohydrate / immunology
  • Chemistry Techniques, Synthetic
  • Drug Compounding
  • Female
  • Galactosylceramides / chemical synthesis
  • Galactosylceramides / chemistry*
  • Galactosylceramides / immunology*
  • Immunity, Cellular / immunology
  • Immunity, Humoral / immunology
  • Immunization
  • Liposomes / chemistry*
  • Mice, Inbred C57BL
  • Phenotype

Substances

  • Antigens, Tumor-Associated, Carbohydrate
  • Galactosylceramides
  • Liposomes
  • Tn antigen
  • alpha-galactosylceramide