title: Increasing cellular immunogenicity to peptide-based vaccine candidates using a fluorocarbon antigen delivery system.
abstract: 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.
authors.affiliation: Immune Targeting Systems, 2 Royal College Street, London, NW1 0NH, UK. Electronic address: james.francis@its-innovation.com.
authors.forename: James N
authors.initials: JN
authors.lastname: Francis
authors.affiliation: Immune Targeting Systems, 2 Royal College Street, London, NW1 0NH, UK.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Thaburet
authors.affiliation: Laboratoire d'Innovation Thérapeutique, UMR7200 CNRS, Université de Strasbourg, LabexMedalis, Faculté de Pharmacie, 74 route du Rhin, 67412 Illkirch, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonnet
authors.affiliation: Immune Targeting Systems, 2 Royal College Street, London, NW1 0NH, UK.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Sizer
authors.affiliation: Immune Targeting Systems, 2 Royal College Street, London, NW1 0NH, UK.
authors.forename: Carlton B
authors.initials: CB
authors.lastname: Brown
authors.affiliation: Immune Targeting Systems, 2 Royal College Street, London, NW1 0NH, UK.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Georges
mesh_terms: D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005466:Fluorocarbons; D007111:Immunity, Cellular; D007114:Immunization; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008823:Micelles; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D059748:Proteolysis; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D005466:Fluorocarbons; D008823:Micelles; D010455:Peptides; D022223:Vaccines, Subunit
keywords: Delivery system; Fluoropeptide; Immunogenicity; Vaccine