title: IgG-mediated anaphylaxis to a synthetic long peptide vaccine containing a B cell epitope can be avoided by slow-release formulation.
abstract: Synthetic long peptides (SLP) are a promising vaccine modality to induce therapeutic T cell responses in patients with chronic infections and tumors. We studied different vaccine formulations in mice using SLP derived from carcinoembryonic Ag. We discovered that one of the SLP contains a linear Ab epitope in combination with a CD4 epitope. Repeated vaccination with this carcinoembryonic Ag SLP in mice shows improved T cell responses and simultaneously induced high titers of peptide-specific Abs. These Abs resulted in unexpected anaphylaxis after a third or subsequent vaccinations with the SLP when formulated in saline. Administration of low SLP doses in the slow-release vehicle IFA prevented the anaphylaxis after repeated vaccination. This study underscores both the immunogenicity of SLP vaccination, for inducing T cell as well as B cell responses, and the necessity of safe administration routes.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;
authors.forename: Esther D
authors.initials: ED
authors.lastname: Quakkelaar
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;
authors.forename: Marieke F
authors.initials: MF
authors.lastname: Fransen
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;
authors.forename: Wendy W C
authors.initials: WW
authors.lastname: van Maren
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;
authors.forename: Joost
authors.initials: J
authors.lastname: Vaneman
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;
authors.forename: Nikki M
authors.initials: NM
authors.lastname: Loof
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; and.
authors.forename: Sandra H
authors.initials: SH
authors.lastname: van Heiningen
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; and.
authors.forename: J Sjef
authors.initials: JS
authors.lastname: Verbeek
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;
authors.forename: Ferry
authors.initials: F
authors.lastname: Ossendorp
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; ISA Pharmaceuticals, 2333 CH Leiden, The Netherlands c.melief@lumc.nl.
authors.forename: Cornelis J M
authors.initials: CJ
authors.lastname: Melief
mesh_terms: D000707:Anaphylaxis / Q000276:immunology / Q000517:prevention & control*; D000818:Animals; D002272:Carcinoembryonic Antigen / Q000276:immunology / Q000494:pharmacology*; D003692:Delayed-Action Preparations / Q000494:pharmacology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology / Q000494:pharmacology*; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010455:Peptides / Q000276:immunology / Q000494:pharmacology*; D014611:Vaccination / Q000379:methods; D014612:Vaccines / Q000494:pharmacology*
chemical_list: D002272:Carcinoembryonic Antigen; D003692:Delayed-Action Preparations; D018985:Epitopes, B-Lymphocyte; D007074:Immunoglobulin G; D010455:Peptides; D014612:Vaccines