title: Novel immunogenic peptides elicit systemic anaphylaxis in mice: implications for peptide vaccines.
abstract: Peptide-based therapies are showing increasing potential for the development of vaccines and in the treatment of many important diseases. We previously reported two peptide conjugate vaccines that protected mice against pneumococcal disease. During this study, we observed an unexpected phenomenon; several vaccine candidates induced a rapid, fatal anaphylaxis after booster injection of the peptide conjugate. Further investigation indicated the reaction was mediated by the production of peptide-specific IgE and the release of histamine. Notably, among seven peptides tested, all of which bound the same mAb that selected them from a phage library, only four elicited this severe reaction. Sequence alignment analysis of all peptides revealed unique clusters of acidic amino acid residues in the allergenic peptides. Substitution of the acidic amino acid residues, ED, of peptide MP2 with their amine equivalents, QN, eliminated the anaphylactic effects but did not affect the production of peptide-specific IgG. These results have important implications for both the study of allergens and the development of future peptide-based therapies.
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, United Kingdom.
authors.forename: Claire Mary
authors.initials: CM
authors.lastname: Smith
authors.forename: Peter
authors.initials: P
authors.lastname: Bradding
authors.forename: Daniel Robert
authors.initials: DR
authors.lastname: Neill
authors.forename: Helen
authors.initials: H
authors.lastname: Baxendale
authors.forename: Franco
authors.initials: F
authors.lastname: Felici
authors.forename: Peter William
authors.initials: PW
authors.lastname: Andrew
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D000707:Anaphylaxis / Q000276:immunology* / Q000382:microbiology* / Q000401:mortality; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000378:metabolism; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D006636:Histamine Release / Q000276:immunology; D007117:Immunization, Secondary; D007073:Immunoglobulin E / Q000097:blood; D051379:Mice; D018716:Molecular Mimicry / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D011897:Random Allocation; D013296:Streptococcus pneumoniae / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D010446:Peptide Fragments; D011135:Polysaccharides, Bacterial; D022223:Vaccines, Subunit; C437065:pneumococcal polysaccharide type 6; D007073:Immunoglobulin E; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin