title: Evaluation of the immunogenicity and safety of different doses and formulations of a broad spectrum influenza vaccine (FLU-v) developed by SEEK: study protocol for a single-center, randomized, double-blind and placebo-controlled clinical phase IIb trial.
abstract: Current influenza vaccines, based on antibodies against surface antigens, are unable to provide protection against newly emerging virus strains which differ from the vaccine strains. Therefore the population has to be re-vaccinated annually. It is thus important to develop vaccines which induce protective immunity to a broad spectrum of influenza viruses. This trial is designed to evaluate the immunogenicity and safety of FLU-v, a vaccine composed of four synthetic peptides with conserved epitopes from influenza A and B strains expected to elicit both cell mediated immunity (CMI) and humoral immunity providing protection against a broad spectrum of influenza viruses.
  
  
  
  In a single-center, randomized, double-blind and placebo-controlled phase IIb trial, 222 healthy volunteers aged 18-60 years will be randomized (2:2:1:1) to receive two injections of a suspension of 500 μg FLU-v in saline (arm 1), one dose of emulsified 500 μg FLU-v in Montanide ISA-51 and water for injection (WFI) followed by one saline dose (arm 2), two saline doses (arm 3), or one dose of Montanide ISA-51 and WFI emulsion followed by one saline dose (arm 4). All injections will be given subcutaneously. Primary endpoints are safety and FLU-v induced CMI, evaluated by cytokine production by antigen specific T cell populations (flow-cytometry and ELISA). Secondary outcomes are measurements of antibody responses (ELISA and multiplex), whereas exploratory outcomes include clinical efficacy and additional CMI assays (ELISpot) to show cross-reactivity.
  
  
  
  Broadly protective influenza vaccines able to provide protection against multiple strains of influenza are urgently needed. FLU-v is a promising vaccine which has shown to trigger the cell-mediated immune response. The dosages and formulations tested in this current trial are also estimated to induce antibody response. Therefore, both cellular and humoral immune responses will be evaluated.
  
  
  
  EudraCT number 2015-001932-38 ; retrospectively registered clinicaltrials.gov NCT02962908 (November 7th 2016).
authors.affiliation: University of Groningen, Unit of PharmacoTherapy- Epidemiology & -Economics, Antonius Deusinglaan, 9713 AV, Groningen, The Netherlands. e.van.doorn@rug.nl.
authors.forename: Eva
authors.initials: E
authors.lastname: van Doorn
authors.affiliation: SEEK, Central Point, 45 Beech Street, London, EC2Y 8AD, UK.
authors.forename: Olga
authors.initials: O
authors.lastname: Pleguezuelos
authors.affiliation: University of Groningen, Unit of PharmacoTherapy- Epidemiology & -Economics, Antonius Deusinglaan, 9713 AV, Groningen, The Netherlands.
authors.forename: Heng
authors.initials: H
authors.lastname: Liu
authors.affiliation: SEEK, Central Point, 45 Beech Street, London, EC2Y 8AD, UK.
authors.forename: Ana
authors.initials: A
authors.lastname: Fernandez
authors.affiliation: SEEK, Central Point, 45 Beech Street, London, EC2Y 8AD, UK.
authors.forename: Robin
authors.initials: R
authors.lastname: Bannister
authors.affiliation: SEEK, Central Point, 45 Beech Street, London, EC2Y 8AD, UK.
authors.forename: Gregory
authors.initials: G
authors.lastname: Stoloff
authors.affiliation: Norwegian Institute of Public Health, Department of Infectious Disease Immunology, Oslo, Norway.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Oftung
authors.affiliation: Robert Koch Institute, Berlin, Germany.
authors.forename: Stephen
authors.initials: S
authors.lastname: Norley
authors.affiliation: University Medical Center Groningen, Medical Microbiology, Groningen, The Netherlands.
authors.forename: Anke
authors.initials: A
authors.lastname: Huckriede
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Henderik W
authors.initials: HW
authors.lastname: Frijlink
authors.affiliation: University of Groningen, Unit of PharmacoTherapy- Epidemiology & -Economics, Antonius Deusinglaan, 9713 AV, Groningen, The Netherlands.
authors.forename: Eelko
authors.initials: E
authors.lastname: Hak
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology; D004311:Double-Blind Method; D058501:Enzyme-Linked Immunospot Assay; D000939:Epitopes; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D000071497:Immunogenicity, Vaccine; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D008353:Mannitol / Q000031:analogs & derivatives; D008875:Middle Aged; D009829:Oleic Acids; D009975:Orthomyxoviridae / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D000939:Epitopes; D007252:Influenza Vaccines; D009829:Oleic Acids; D014614:Vaccines, Synthetic; C477385:montanide ISA 51; D008353:Mannitol
keywords: Broadly protection; CMI; Clinical trial; FLU-v; Influenza; Universal; Vaccine