title: T-helper 1 cells elicited by H5N1 vaccination predict seroprotection.
abstract: BACKGROUND
  Vaccination is the best measure to protect the population against a potential influenza H5N1 pandemic, but 2 doses of vaccine are needed to elicit protective immune responses. An immunological marker for H5N1 vaccine effectiveness is needed for early identification of the best vaccine candidate.
  
  
  METHODS
  We conducted a phase I clinical trial of a virosomal H5N1 vaccine adjuvanted with Matrix M. Sixty adult volunteers were vaccinated intramuscularly with 2 doses of either 30 μg hemagglutinin (HA) alone or with 1.5, 7.5, or 30 μg HA and Matrix M adjuvant (50 μg). The humoral response was measured by the hemagglutination inhibition (HI), microneutralization (MN), and single radial hemolysis (SRH) assays, and the CD4(+) T-helper 1 (Th1)-cell response was measured by intracellular staining for the cytokines interleukin 2, interferon γ, and tumor necrosis factor α.
  
  
  RESULTS
  The adjuvanted vaccine effectively induced CD4(+) Th1-cell responses, and the frequency of influenza-specific Th1 cells after the first vaccine dose predicted subsequent HI, MN, and SRH seroprotective responses after the second vaccination.
  
  
  CONCLUSIONS
  These results support early identification of Th1-cell responses as a predictive biomarker for an efficient vaccine response, which could have great implications for early identification of persons with low or no response to vaccine when evaluating future pandemic influenza vaccines.
authors.affiliation: The Gade Institute, Haukeland University Hospital, Bergen, Norway. gabriel.pedersen@gades.uib.no
authors.forename: Gabriel K
authors.initials: GK
authors.lastname: Pedersen
authors.forename: Abdullah S
authors.initials: AS
authors.lastname: Madhun
authors.forename: Lucy
authors.initials: L
authors.lastname: Breakwell
authors.forename: Katja
authors.initials: K
authors.lastname: Hoschler
authors.forename: Haakon
authors.initials: H
authors.lastname: Sjursen
authors.forename: Rishi D
authors.initials: RD
authors.lastname: Pathirana
authors.forename: Jaap
authors.initials: J
authors.lastname: Goudsmit
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Cox
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D016207:Cytokines / Q000097:blood; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D016882:ISCOMs / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D008875:Middle Aged; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D014611:Vaccination; D022721:Vaccines, Virosome / Q000276:immunology; D058425:Vaccines, Virus-Like Particle / Q000276:immunology; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D016207:Cytokines; D016882:ISCOMs; D007252:Influenza Vaccines; D022721:Vaccines, Virosome; D058425:Vaccines, Virus-Like Particle