title: Enhancing the immunogenicity and modulating the fine epitope recognition of antisera to a helical group A streptococcal peptide vaccine candidate from the M protein using lipid-core peptide technology.
abstract: A conserved helical peptide vaccine candidate from the M protein of group A streptococci, p145, has been described. Minimal epitopes within p145 have been defined and an epitope recognized by protective antibodies, but not by autoreactive T cells, has been identified. When administered to mice, p145 has low immunogenicity. Many boosts of peptide are required to achieve a high antibody titre (> 12 800). To attempt to overcome this low immunogenicity, lipid-core peptide technology was employed. Lipid-core peptides (LCP) consist of an oligomeric polylysine core, with multiple copies of the peptide of choice, conjugated to a series of lipoamino acids, which acts as an anchor for the antigen. Seven different LCP constructs based on the p145 peptide sequence were synthesized (LCP1-->LCP7) and the immunogenicity of the compounds examined. The most immunogenic constructs contained the longest alkyl side-chains. The number of lipoamino acids in the constructs affected the immunogenicity and spacing between the alkyl side-chains increased immunogenicity. An increase in immunogenicity (enzyme-linked immunosorbent assay (ELISA) titres) of up to 100-fold was demonstrated using this technology and some constructs without adjuvant were more immunogenic than p145 administered with complete Freund's adjuvant (CFA). The fine specificity of the induced antibody response differed for the different constructs but one construct, LCP4, induced antibodies of identical fine specificity to those found in endemic human serum. Opsonic activity of LCP4 antisera was more than double that of p145 antisera. These data show the potential for LCP technology to both enhance immunogenicity of complex peptides and to focus the immune response towards or away from critical epitopes.
authors.affiliation: The Cooperative ResearchCentre for Vaccine Technology, The Queensland Institute of Medical Research, Royal Brisbane Hospital, Brisbane, Australia.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Hayman
authors.forename: Istvan
authors.initials: I
authors.lastname: Toth
authors.forename: Nicholas
authors.initials: N
authors.lastname: Flinn
authors.forename: Martin
authors.initials: M
authors.lastname: Scanlon
authors.forename: Michael F
authors.initials: MF
authors.lastname: Good
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000276:immunology*; D001709:Biotechnology; D002352:Carrier Proteins / Q000737:chemistry* / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000276:immunology; D005260:Female; D005620:Freund's Adjuvant / Q000276:immunology; D008074:Lipoproteins / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009895:Opsonin Proteins / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011107:Polylysine / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D022541:Streptococcal Vaccines / Q000737:chemistry / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D018985:Epitopes, B-Lymphocyte; D008074:Lipoproteins; D009895:Opsonin Proteins; D010446:Peptide Fragments; D022541:Streptococcal Vaccines; C014689:streptococcal M protein; D011107:Polylysine; D005620:Freund's Adjuvant