Development of conformational mimetics of conserved Streptococcus pyogenes minimal epitope as vaccine candidates.
One of the factors responsible for the poor immunogenicity of synthetic peptide antigens is the lack of conformational integrity. Embedding the minimal epitopes in helix-promoting peptide sequences has successfully enhanced the immunogenicity of the epitopes derived from the alpha-helical regions of the M protein of group A streptococci (Streptococcus pyogenes, GAS). However, the introduction of "foreign" peptide sequences is believed to have an unfavourable impact on the antigen specificity. In the current study, we employed a non-peptide approach, using topological carbohydrate templates, to induce helical conformation of the peptide antigens. Utilized together with the advances of the lipid core peptide system and chemoselective ligation, five GAS vaccine candidates incorporating the minimal epitope J14i (ASREAKKQVEKALE) were synthesized with high purity. Circular dichroism studies indicated that the template-assembled peptides formed alpha-helix bundles. This atom-economic strategy also reduces the complexity and cost of vaccine production by simply reducing the peptide epitope size.
Zhong
Wei
W
The School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia.
Skwarczynski
Mariusz
M
Toth
Istvan
I
D000276:Adjuvants, Immunologic / Q000737:chemistry; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000276:immunology; D002241:Carbohydrates / Q000737:chemistry; D002352:Carrier Proteins / Q000737:chemistry* / Q000276:immunology; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D000939:Epitopes; D055666:Lipopeptides / Q000737:chemistry; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry* / Q000276:immunology / Q000302:isolation & purification; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D021241:Spectrometry, Mass, Electrospray Ionization; D013290:Streptococcal Infections / Q000517:prevention & control; D022541:Streptococcal Vaccines / Q000737:chemistry / Q000191:economics / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000737:chemistry / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000191:economics / Q000276:immunology
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002241:Carbohydrates; D002352:Carrier Proteins; D000939:Epitopes; D055666:Lipopeptides; D010455:Peptides; D022541:Streptococcal Vaccines; D014614:Vaccines, Synthetic; C014689:streptococcal M protein