Development of a liposaccharide-based delivery system and its application to the design of group A streptococcal vaccines

Pavla Simerska; Abu-Baker M Abdel-Aal; Yoshio Fujita; Peter M Moyle; Ross P McGeary; Michael R Batzloff; Colleen Olive; Michael F Good; Istvan Toth

doi:10.1021/jm701410p

Development of a liposaccharide-based delivery system and its application to the design of group A streptococcal vaccines

J Med Chem. 2008 Mar 13;51(5):1447-52. doi: 10.1021/jm701410p. Epub 2008 Feb 16.

Authors

Pavla Simerska¹, Abu-Baker M Abdel-Aal, Yoshio Fujita, Peter M Moyle, Ross P McGeary, Michael R Batzloff, Colleen Olive, Michael F Good, Istvan Toth

Affiliation

¹ School of Molecular and Microbial Sciences , The University of Queensland, St Lucia 4072, Queensland, Australia.

PMID: 18278857
DOI: 10.1021/jm701410p

Abstract

Group A streptococcus (GAS) is associated with many human diseases, ranging in severity from benign to life-threatening. A promising strategy for developing vaccines against GAS involves the use of carbohydrates as carriers for peptide antigens. This study describes the optimized synthesis of d-glucose and d-galactose derived carriers, bearing an adipate linker and four tert-butoxycarbonyl protected aminopropyl groups. Prophylactic GAS vaccine candidates were synthesized by conjugating multiple copies of a single GAS M protein derived peptide antigen (either J8 or J14) onto the carbohydrate carriers. These antigens contain peptide sequences, which are highly conserved and offer the potential to prevent infections caused by up to 70% of GAS strains. Lipophilic amino acids were also conjugated to the d-glucose anomeric carbon to produce a self-adjuvanting liposaccharide vaccine. High serum IgG antibody titers against each of the incorporated peptide epitopes were detected following subcutaneous immunization of B10.BR (H-2 (k)) mice with the liposaccharide vaccine candidates.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, Bacterial / chemistry*
Antigens, Bacterial / immunology
Bacterial Outer Membrane Proteins / chemistry*
Bacterial Outer Membrane Proteins / immunology
Bacterial Proteins / chemistry
Bacterial Proteins / immunology
Carrier Proteins / chemistry*
Carrier Proteins / immunology
Drug Carriers
Enzyme-Linked Immunosorbent Assay
Epitopes
Female
Galactose / chemistry*
Glucose / chemistry*
Glycopeptides / chemistry
Glycopeptides / immunology
Immunoglobulin G / biosynthesis
Lauric Acids / chemistry*
Mice
Peptide Fragments / chemistry
Peptide Fragments / immunology
Streptococcal Vaccines / administration & dosage
Streptococcal Vaccines / chemical synthesis*
Streptococcal Vaccines / chemistry
Streptococcal Vaccines / immunology
Streptococcus pyogenes / immunology*
Vaccines, Subunit

Substances

Antigens, Bacterial
Bacterial Outer Membrane Proteins
Bacterial Proteins
Carrier Proteins
Drug Carriers
Epitopes
Glycopeptides
Immunoglobulin G
Lauric Acids
Peptide Fragments
Streptococcal Vaccines
Vaccines, Subunit
peptide 145, Streptococcus
streptococcal M protein
Glucose
Galactose