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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.
AuthorsJames N Francis, Jean-François Thaburet, Dominique Bonnet, Philip J Sizer, Carlton B Brown, Bertrand Georges
JournalVaccine (Vaccine) Vol. 33 Issue 8 Pg. 1071-6 (Feb 18 2015) ISSN: 1873-2518 [Electronic] Netherlands
PMID25573036 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Ltd. All rights reserved.
Chemical References
  • Adjuvants, Immunologic
  • Cytokines
  • Fluorocarbons
  • Micelles
  • Peptides
  • Vaccines, Subunit
Topics
  • Adjuvants, Immunologic
  • Amino Acid Sequence
  • Animals
  • Cytokines (biosynthesis)
  • Female
  • Fluorocarbons
  • Immunity, Cellular
  • Immunization
  • Lymphocyte Activation (immunology)
  • Mice
  • Micelles
  • Molecular Sequence Data
  • Peptides (chemistry, immunology)
  • Proteolysis
  • Vaccines, Subunit (administration & dosage, immunology)

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