title: Characterization of a branched lipopeptide candidate vaccine against influenza A/Puerto Rico 8/34 which is recognized by human B and T-cell immune responses.
abstract: The use of synthetic peptides as immunogens represents an exciting alternative to traditional vaccines. However, to date most of these synthetic peptides are not highly immunogenic. The lack of immunogenicity might be addressed by conjugation between T or B cell epitopes with universal or immunodominant T-helper epitopes. The construction of lipidated peptides, branched peptides, or designs combining both of these elements might enhance the immunogenicity, as they might target Toll-Like Receptors and/or mimic the 3-dimensional structure of epitopes within the native protein. Herein, a recognized peptide immunogen based on the hemagglutinin protein of A/Puerto Rico/8/34 was chosen as a backbone and modified to evaluate if the construction of branched peptides, lipidation, the addition of cysteine residues, or mutations could indeed alter epitope reactivity. Screening the different designs with various antibody binding and cellular assays revealed that combining a branched design with the addition of lipid moieties greatly enhanced the immunoreactivity.
authors.affiliation: Infectious Disease and Vaccine Research Center, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Canada. aazizi@uottawa.ca
authors.forename: Liz
authors.initials: L
authors.lastname: Samayoa
authors.forename: Francisco
authors.initials: F
authors.lastname: Diaz-Mitoma
authors.forename: Ali
authors.initials: A
authors.lastname: Azizi
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000138:chemical synthesis / Q000276:immunology*; D055666:Lipopeptides / Q000138:chemical synthesis / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D013601:T-Lymphocytes / Q000276:immunology*; D022223:Vaccines, Subunit / Q000138:chemical synthesis / Q000276:immunology*; D010948:Viral Plaque Assay
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D055666:Lipopeptides; D022223:Vaccines, Subunit