Synthesis of a highly pure lipid core peptide based self-adjuvanting triepitopic group A streptococcal vaccine, and subsequent immunological evaluation.
We have developed a highly pure, self-adjuvanting, triepitopic Group A Streptococcal vaccine based on the lipid core peptide system, a vaccine delivery system incorporating lipidic adjuvant, carrier, and peptide epitopes into a single molecular entity. Vaccine synthesis was performed using native chemical ligation. Due to the attachment of a highly lipophilic adjuvant, addition of 1% (w/v) sodium dodecyl sulfate was necessary to enhance peptide solubility in order to enable ligation. The vaccine was synthesized in three steps to yield a highly pure product (97.7% purity) with an excellent overall yield. Subcutaneous immunization of B10.BR (H-2(k)) mice with the synthesized vaccine, with or without the addition of complete Freund's adjuvant, elicited high serum IgG antibody titers against each of the incorporated peptide epitopes.
Moyle
Peter M
PM
School of Pharmacy, The University of Queensland, St. Lucia 4072, Queensland, Australia.
Olive
Colleen
C
Ho
Mei-Fong
MF
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; D002352:Carrier Proteins / Q000737:chemistry* / Q000276:immunology; D000939:Epitopes; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D022541:Streptococcal Vaccines / Q000138:chemical synthesis* / Q000276:immunology; D013297:Streptococcus pyogenes / Q000276:immunology*; D014611:Vaccination; D022223:Vaccines, Subunit / Q000138:chemical synthesis / Q000276:immunology
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D000939:Epitopes; D007074:Immunoglobulin G; D008055:Lipids; D010455:Peptides; D022541:Streptococcal Vaccines; D022223:Vaccines, Subunit; C014689:streptococcal M protein