Increasing cellular immunogenicity to peptide-based vaccine candidates using a fluorocarbon antigen delivery system.
Fiche publication
Date publication
février 2015
Journal
Vaccine
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BONNET Dominique
Tous les auteurs :
Francis JN, Thaburet JF, Bonnet D, Sizer PJ, Brown CB, Georges B
Lien Pubmed
Résumé
Traditionally, synthetic peptide vaccines for infectious diseases and cancer require adjuvants to achieve optimal immunogenicity. Here we describe a novel method of peptide modification using a fluorocarbon chain which can substantially increase peptide-specific cellular immune responses in the absence of adjuvant. We demonstrate that fluorocarbon-modified peptides (fluoropeptides) derived from HIV, influenza and hepatitis C virus can significantly increase interferon gamma ELISpot responses against cytotoxic and T-helper epitopes compared to unmodified peptides or lipopeptides in mice. Increases in both T-helper1 and T-helper2 cytokines are observed. Fluoropeptides show enhanced ability of the antigen to persist at the site of administration and persistence is associated with a prolonged and elevated immune response. Additionally we demonstrate that fluoropeptides have increased proteolytic resistance thereby potentially supporting their increased half-life in vivo. Fluorocarbon-modification of peptides provides a valuable tool for increasing cellular immunogenicity of vaccines for infectious diseases and cancer without requirement for traditional adjuvants.
Mots clés
Adjuvants, Immunologic, Amino Acid Sequence, Animals, Cytokines, biosynthesis, Female, Fluorocarbons, Immunity, Cellular, Immunization, Lymphocyte Activation, immunology, Mice, Micelles, Molecular Sequence Data, Peptides, chemistry, Proteolysis, Vaccines, Subunit, administration & dosage
Référence
Vaccine. 2015 Feb 18;33(8):1071-6