title: Method for the synthesis of multi-epitopic Streptococcus pyogenes lipopeptide vaccines using native chemical ligation.
abstract: The aim of this study was to investigate methods for the synthesis of highly pure, well-characterized analogues of the lipid core peptide (LCP) system. Difficulties synthesizing and purifying conventional LCP systems have led to the requirement for a technique to produce highly pure, LCP-based vaccines for potential use in human clinical trials. The current study describes methods for the attachment of lipophilic adjuvants onto multi-epitopic peptide vaccines. Described is the synthesis, using native chemical ligation, of a highly pure, tri-epitopic, group A streptococcal (GAS) lipopeptide vaccine candidate. Intranasal immunization of the described tri-epitopic GAS lipopeptide with the mucosal adjuvant cholera toxin B subunit induced high serum IgG antibody titers specific for each of the incorporated peptide epitopes.
authors.affiliation: School of Pharmacy and School of Molecular and Microbial Sciences (SMMS), University of Queensland, St. Lucia, QLD, Australia.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Moyle
authors.forename: Colleen
authors.initials: C
authors.lastname: Olive
authors.forename: Mei-Fong
authors.initials: MF
authors.lastname: Ho
authors.forename: Melinda
authors.initials: M
authors.lastname: Burgess
authors.forename: Levente
authors.initials: L
authors.lastname: Karpati
authors.forename: Michael F
authors.initials: MF
authors.lastname: Good
authors.forename: Istvan
authors.initials: I
authors.lastname: Toth
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D002625:Chemistry, Organic / Q000379:methods*; D002772:Cholera Toxin / Q000494:pharmacology; D003545:Cysteine / Q000737:chemistry; D004353:Drug Evaluation, Preclinical / Q000379:methods; D000939:Epitopes; D005260:Female; D007106:Immune Sera; D007074:Immunoglobulin G / Q000032:analysis; D008074:Lipoproteins / Q000138:chemical synthesis / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D022541:Streptococcal Vaccines / Q000138:chemical synthesis* / Q000276:immunology / Q000494:pharmacology; D013297:Streptococcus pyogenes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D000939:Epitopes; D007106:Immune Sera; D007074:Immunoglobulin G; D008074:Lipoproteins; D022541:Streptococcal Vaccines; D014614:Vaccines, Synthetic; D002772:Cholera Toxin; D003545:Cysteine