Development of a liposaccharide-based delivery system and its application to the design of group A streptococcal vaccines.
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.
Simerska
Pavla
P
School of Molecular and Microbial Sciences , The University of Queensland, St Lucia 4072, Queensland, Australia.
Abdel-Aal
Abu-Baker M
AB
Fujita
Yoshio
Y
Moyle
Peter M
PM
McGeary
Ross P
RP
Batzloff
Michael R
MR
Olive
Colleen
C
Good
Michael F
MF
Toth
Istvan
I
D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000276:immunology; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology; D002352:Carrier Proteins / Q000737:chemistry* / Q000276:immunology; D004337:Drug Carriers; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005260:Female; D005690:Galactose / Q000737:chemistry*; D005947:Glucose / Q000737:chemistry*; D006020:Glycopeptides / Q000737:chemistry / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007850:Lauric Acids / Q000737:chemistry*; D051379:Mice; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D022541:Streptococcal Vaccines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D013297:Streptococcus pyogenes / Q000276:immunology*; D022223:Vaccines, Subunit
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D004337:Drug Carriers; D000939:Epitopes; D006020:Glycopeptides; D007074:Immunoglobulin G; D007850:Lauric Acids; D010446:Peptide Fragments; D022541:Streptococcal Vaccines; D022223:Vaccines, Subunit; C089007:peptide 145, Streptococcus; C014689:streptococcal M protein; D005947:Glucose; D005690:Galactose