title: Preliminary assessment of the efficacy of a T-cell-based influenza vaccine, MVA-NP+M1, in humans.
abstract: BACKGROUND
  The novel influenza vaccine MVA-NP+M1 is designed to boost cross-reactive T-cell responses to internal antigens of the influenza A virus that are conserved across all subtypes, providing protection against both influenza disease and virus shedding against all influenza A viruses. Following a phase 1 clinical study that demonstrated vaccine safety and immunogenicity, a phase 2a vaccination and influenza challenge study has been conducted in healthy adult volunteers.
  
  
  METHODS
  Volunteers with no measurable serum antibodies to influenza A/Wisconsin/67/2005 received either a single vaccination with MVA-NP+M1 or no vaccination. T-cell responses to the vaccine antigens were measured at enrollment and again prior to virus challenge. All volunteers underwent intranasal administration of influenza A/Wisconsin/67/2005 while in a quarantine unit and were monitored for symptoms of influenza disease and virus shedding.
  
  
  RESULTS
  Volunteers had a significantly increased T-cell response to the vaccine antigens following a single dose of the vaccine, with an increase in cytolytic effector molecules. Intranasal influenza challenge was undertaken without safety issues. Two of 11 vaccinees and 5 of 11 control subjects developed laboratory-confirmed influenza (symptoms plus virus shedding). Symptoms of influenza were less pronounced in the vaccinees and there was a significant reduction in the number of days of virus shedding in those vaccinees who developed influenza (mean, 1.09 days in controls, 0.45 days in vaccinees, P = .036).
  
  
  CONCLUSIONS
  This study provides the first demonstration of clinical efficacy of a T-cell-based influenza vaccine and indicates that further clinical development should be undertaken.
  
  
  BACKGROUND
  NCT00993083.
authors.affiliation: Jenner Institute, University of Oxford, UK.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Lillie
authors.forename: Tamara K
authors.initials: TK
authors.lastname: Berthoud
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Powell
authors.forename: Teresa
authors.initials: T
authors.lastname: Lambe
authors.forename: Caitlin
authors.initials: C
authors.lastname: Mullarkey
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Spencer
authors.forename: Matthew
authors.initials: M
authors.lastname: Hamill
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Peng
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Blais
authors.forename: Christopher J A
authors.initials: CJ
authors.lastname: Duncan
authors.forename: Susanne H
authors.initials: SH
authors.lastname: Sheehy
authors.forename: Tom
authors.initials: T
authors.lastname: Havelock
authors.forename: Saul N
authors.initials: SN
authors.lastname: Faust
authors.forename: Rob Lambkin
authors.initials: RL
authors.lastname: Williams
authors.forename: Anthony
authors.initials: A
authors.lastname: Gilbert
authors.forename: John
authors.initials: J
authors.lastname: Oxford
authors.forename: Tao
authors.initials: T
authors.lastname: Dong
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D015789:HLA-A2 Antigen; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D007371:Interferon-gamma; D008875:Middle Aged; D019590:Nucleocapsid Proteins; D010865:Pilot Projects; D016601:RNA-Binding Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology; D017201:Virus Shedding
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D015789:HLA-A2 Antigen; D007252:Influenza Vaccines; C488936:M1 protein, Influenza A virus; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; D014763:Viral Matrix Proteins; D007371:Interferon-gamma