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Development of a liposaccharide-based delivery system and its application to the design of group A streptococcal vaccines.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 2008 Mar 13; Vol. 51 (5), pp. 1447-52. Date of Electronic Publication: 2008 Feb 16. - Publication Year :
- 2008
-
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.
- Subjects :
- Animals
Antigens, Bacterial immunology
Bacterial Outer Membrane Proteins immunology
Bacterial Proteins chemistry
Bacterial Proteins immunology
Carrier Proteins immunology
Drug Carriers
Enzyme-Linked Immunosorbent Assay
Epitopes
Female
Glycopeptides chemistry
Glycopeptides immunology
Immunoglobulin G biosynthesis
Mice
Peptide Fragments chemistry
Peptide Fragments immunology
Streptococcal Vaccines administration & dosage
Streptococcal Vaccines chemistry
Streptococcal Vaccines immunology
Vaccines, Subunit
Antigens, Bacterial chemistry
Bacterial Outer Membrane Proteins chemistry
Carrier Proteins chemistry
Galactose chemistry
Glucose chemistry
Lauric Acids chemistry
Streptococcal Vaccines chemical synthesis
Streptococcus pyogenes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2623
- Volume :
- 51
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 18278857
- Full Text :
- https://doi.org/10.1021/jm701410p