title: Matrix M H5N1 Vaccine Induces Cross-H5 Clade Humoral Immune Responses in a Randomized Clinical Trial and Provides Protection from Highly Pathogenic Influenza Challenge in Ferrets.
abstract: METHODS
  Highly pathogenic avian influenza (HPAI) viruses constitute a pandemic threat and the development of effective vaccines is a global priority. Sixty adults were recruited into a randomized clinical trial and were intramuscularly immunized with two virosomal vaccine H5N1 (NIBRG-14) doses (21 days apart) of 30 μg HA alone or 1.5, 7.5 or 30 μg HA adjuvanted with Matrix M. The kinetics and longevity of the serological responses against NIBRG-14 were determined by haemagglutination inhibition (HI), single radial haemolysis (SRH), microneutralization (MN) and ELISA assays. The cross-H5 clade responses in sera were determined by HI and the antibody-secreting (ASC) cell ELISPOT assays. The protective efficacy of the vaccine against homologous HPAI challenge was evaluated in ferrets.
  
  
  RESULTS
  The serological responses against the homologous and cross-reactive strains generally peaked one week after the second dose, and formulation with Matrix M augmented the responses. The NIBRG-14-specific seroprotection rates fell significantly by six months and were low against cross-reactive strains although the adjuvant appeared to prolong the longevity of the protective responses in some subjects. By 12 months post-vaccination, nearly all vaccinees had NIBRG-14-specific antibody titres below the protective thresholds. The Matrix M adjuvant was shown to greatly improve ASC and serum IgG responses following vaccination. In a HPAI ferret challenge model, the vaccine protected the animals from febrile responses, severe weight loss and local and systemic spread of the virus.
  
  
  CONCLUSIONS
  Our findings show that the Matrix M-adjuvanted virosomal H5N1 vaccine is a promising pre-pandemic vaccine candidate.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00868218.
authors.affiliation: Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Research and Development, Haukeland University Hospital, Bergen, Norway; Jebsen Centre for Influenza Vaccine Research, University of Bergen, Bergen, Norway.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Cox
authors.affiliation: National Institute for Biological Standards and Control (NIBSC), Potters Bar, United Kingdom.
authors.forename: Diane
authors.initials: D
authors.lastname: Major
authors.affiliation: Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Pedersen
authors.affiliation: Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Research and Development, Haukeland University Hospital, Bergen, Norway; Jebsen Centre for Influenza Vaccine Research, University of Bergen, Bergen, Norway.
authors.forename: Rishi D
authors.initials: RD
authors.lastname: Pathirana
authors.affiliation: Respiratory Unit, Public Health England (PHE) Colindale, London, United Kingdom.
authors.forename: Katja
authors.initials: K
authors.lastname: Hoschler
authors.affiliation: National Institute for Biological Standards and Control (NIBSC), Potters Bar, United Kingdom.
authors.forename: Kate
authors.initials: K
authors.lastname: Guilfoyle
authors.affiliation: National Institute for Biological Standards and Control (NIBSC), Potters Bar, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Roseby
authors.affiliation: Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Research and Development, Haukeland University Hospital, Bergen, Norway; Jebsen Centre for Influenza Vaccine Research, University of Bergen, Bergen, Norway.
authors.forename: Geir
authors.initials: G
authors.lastname: Bredholt
authors.affiliation: Department of Research and Development, Haukeland University Hospital, Bergen, Norway.
authors.forename: Jörg
authors.initials: J
authors.lastname: Assmus
authors.affiliation: Respiratory Unit, Public Health England (PHE) Colindale, London, United Kingdom.
authors.forename: Lucy
authors.initials: L
authors.lastname: Breakwell
authors.affiliation: Istituto Superiore di Sanita (ISS), Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Campitelli
authors.affiliation: Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway; Section for Infectious Diseases, Medical Department, Haukeland University Hospital, Bergen, Norway.
authors.forename: Haakon
authors.initials: H
authors.lastname: Sjursen
mesh_terms: D000328:Adult; D000818:Animals; D005260:Female; D005289:Ferrets; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology / Q000494:pharmacology*; D007251:Influenza, Human / Q000276:immunology*; D008875:Middle Aged; D055815:Young Adult
chemical_list: D007252:Influenza Vaccines