title: A novel peptide-based pan-influenza A vaccine: a double blind, randomised clinical trial of immunogenicity and safety.
abstract: BACKGROUND
  FP-01.1 is a novel synthetic influenza A vaccine consisting of six fluorocarbon-modified 35-mer peptides that encapsulate multiple CD4+ and CD8+ T-cell epitopes and is designed to induce an immune response across a broad population.
  
  
  METHODS
  FP-01.1 was evaluated for safety and immunogenicity in a randomised, double-blind, placebo-controlled, dose-escalation, phase I clinical study in healthy adult volunteers (n=49). IFNγ ELISpot assays and multicolour flow cytometry were used to characterise the immune response.
  
  
  RESULTS
  FP-01.1 was safe and well tolerated at all doses tested with a similar adverse event profile in actively vaccinated subjects compared with controls. Maximum immunogenicity was in the 150 μg/peptide dose group where a robust response (243 spots/million PBMC) was demonstrated in 75% subjects compared with 0% in placebo controls. All six peptides were immunogenic. FP-01.1 induced dual CD4+ and CD8+ T cell responses and vaccine-specific T cells cross-recognise divergent influenza strains.
  
  
  CONCLUSIONS
  This first-in-human study showed that FP-01.1 has an acceptable safety and tolerability profile and generated robust anti-viral T cell responses in a high proportion of subjects tested. The results support the further clinical testing of FP-01.1 prior to clinical, proof-of-concept, live viral challenge studies.
authors.affiliation: Immune Targeting Systems Ltd., London, NW1 0NH, UK.
authors.forename: James N
authors.initials: JN
authors.lastname: Francis
authors.affiliation: Immune Targeting Systems Ltd., London, NW1 0NH, UK. Electronic address: campbell.bunce@its-innovation.com.
authors.forename: Campbell J
authors.initials: CJ
authors.lastname: Bunce
authors.affiliation: Immune Targeting Systems Ltd., London, NW1 0NH, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Horlock
authors.affiliation: Immune Targeting Systems Ltd., London, NW1 0NH, UK.
authors.forename: Jeannette M
authors.initials: JM
authors.lastname: Watson
authors.affiliation: Hammersmith Medicines Research Ltd., London, NW10 7EW, UK.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Warrington
authors.affiliation: Immune Targeting Systems Ltd., London, NW1 0NH, UK.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Georges
authors.affiliation: Immune Targeting Systems Ltd., London, NW1 0NH, UK.
authors.forename: Carlton B
authors.initials: CB
authors.lastname: Brown
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003429:Cross Reactions; D004311:Double-Blind Method; D058501:Enzyme-Linked Immunospot Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D018984:Epitopes, T-Lymphocyte; D007252:Influenza Vaccines; D022223:Vaccines, Subunit; D007371:Interferon-gamma
keywords: Fluoropeptides; Immunogenicity; Influenza; Peptides; Safety; T cells; Vaccine