title: Evaluating the immunogenicity and safety of a BiondVax-developed universal influenza vaccine (Multimeric-001) either as a standalone vaccine or as a primer to H5N1 influenza vaccine: Phase IIb study protocol.
abstract: BACKGROUND
  Influenza is a major respiratory viral infection of humans with high mortality and morbidity rates and profound economic impact. Although influenza vaccines are generally updated yearly to match the viruses expected in the coming season, genetic mutation and reassortment can result in unexpected novel strains. Therefore, it is important to develop universal vaccines inducing protective immunity to such strains before they appear. This clinical trial is designed to evaluate the safety and immunogenicity of Multimeric-001 (M-001), which contains conserved epitopes of influenza A and B. M-001 is able to induce both humoral and cellular immunity and provides broad strain coverage.
  
  
  METHODS
  In a multicenter, randomized, double-blind, and controlled phase IIb trial, 222 healthy volunteers aged 18 to 60 years will be randomized into 3 groups (1:1:1) to receive either 2 intramuscular injections of 0.5 mg M-001 (arm 1), 1.0 mg M-001 (arm 2), or saline (arm 3-placebo), before receiving an investigational (whole virus, inactivated, aluminum phosphate gel [AlPO4]-adjuvanted) prepandemic influenza vaccine (H5N1). Primary outcomes are safety and cellular immune responses (cell-mediated immunity [CMI]) induced by M-001, evaluated by multiparametric flow cytometry of intracellular cytokines. The secondary outcome is the serum hemagglutination inhibition (HAI) titer toward the H5N1 vaccine strain. Additionally, exploratory outcomes include evaluation of CMI by quantitative reverse transcription polymerase chain reaction of cytokine mRNA, HAI titers toward H5-drifted strains, serum single radial hemolysis titers toward the H5N1 study vaccine, and the association between CMI markers and antibody response.
  
  
  CONCLUSIONS
  There is a need for influenza vaccines that give the population a broader protection against multiple strains of influenza virus. M-001 might be such vaccine which will be tested in this current trial as a standalone vaccine and as a pandemic primer. Both cellular and humoral immune responses will be evaluated.
  
  
  BACKGROUND
  EudraCT number: 2015-001979-46.
authors.affiliation: Unit of Pharmacotherapy, -Epidemiology and -Economics, University of Groningen, Groningen, The Netherlands BiondVax Pharmaceuticals Ltd, Ness Ziona, Israel Division of Virology, National Center for Epidemiology, Budapest, Hungary Robert Koch Institute, Berlin, Germany Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Eva
authors.initials: E
authors.lastname: van Doorn
authors.forename: Heng
authors.initials: H
authors.lastname: Liu
authors.forename: Tamar
authors.initials: T
authors.lastname: Ben-Yedidia
authors.forename: Shimon
authors.initials: S
authors.lastname: Hassin
authors.forename: Ildiko
authors.initials: I
authors.lastname: Visontai
authors.forename: Stephen
authors.initials: S
authors.lastname: Norley
authors.forename: Henderik W
authors.initials: HW
authors.lastname: Frijlink
authors.forename: Eelko
authors.initials: E
authors.lastname: Hak
mesh_terms: D000293:Adolescent; D000328:Adult; D016207:Cytokines / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005434:Flow Cytometry; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology; D009981:Influenza B virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D012107:Research Design; D055815:Young Adult
chemical_list: D016207:Cytokines; D007252:Influenza Vaccines