Synthesis and immunological evaluation of self-adjuvanting glycolipopeptide vaccine candidates

Bioorg Med Chem. 2008 Oct 1;16(19):8907-13. doi: 10.1016/j.bmc.2008.08.064. Epub 2008 Aug 29.

Abstract

Synthesis of four glycolipids with different number of lauroyl groups on glucose or cellobiose as scaffolds is described. Their immunological evaluations either admixed with or covalently linked to J8, a peptide antigen derived from the C-terminus of the antiphagocytic M-protein of group A streptococcus, are also investigated. Administration of mixtures of J8 and glycolipids to B10BR (H-2(k)) mice induced low-levels of J8-specific IgG antibodies. While glycolipopeptides, in which J8 was covalently linked to the synthetic glycolipids, demonstrated high-levels of antibody titers comparable with the co-administration of these glycolipopeptides with complete Freund's adjuvant, suggesting clearly the strong potency of the synthesized glycolipids as self-adjuvanting moieties.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Bacterial / immunology
  • Antigens, Bacterial / metabolism
  • Bacterial Outer Membrane Proteins / immunology
  • Bacterial Outer Membrane Proteins / metabolism
  • Bacterial Vaccines / administration & dosage*
  • Bacterial Vaccines / immunology
  • Bacterial Vaccines / pharmacology
  • Carrier Proteins / immunology
  • Carrier Proteins / metabolism
  • Female
  • Freund's Adjuvant / administration & dosage*
  • Freund's Adjuvant / immunology
  • Freund's Adjuvant / pharmacology
  • Glycolipids / administration & dosage*
  • Glycolipids / chemical synthesis
  • Glycolipids / pharmacology
  • Glycopeptides / administration & dosage*
  • Glycopeptides / chemical synthesis
  • Glycopeptides / pharmacology
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Mice
  • Molecular Sequence Data
  • Phagocytosis
  • Streptococcus / drug effects*
  • Streptococcus / growth & development
  • Streptococcus / immunology

Substances

  • Antigens, Bacterial
  • Bacterial Outer Membrane Proteins
  • Bacterial Vaccines
  • Carrier Proteins
  • Glycolipids
  • Glycopeptides
  • Immunoglobulin G
  • streptococcal M protein
  • Freund's Adjuvant