title: A T cell-inducing influenza vaccine for the elderly: safety and immunogenicity of MVA-NP+M1 in adults aged over 50 years.
abstract: BACKGROUND
  Current influenza vaccines have reduced immunogenicity and are of uncertain efficacy in older adults. We assessed the safety and immunogenicity of MVA-NP+M1, a viral-vectored influenza vaccine designed to boost memory T cell responses, in a group of older adults.
  
  
  METHODS
  Thirty volunteers (aged 50-85) received a single intramuscular injection of MVA-NP+M1 at a dose of 1·5×10(8) plaque forming units (pfu). Safety and immunogenicity were assessed over a period of one year. The frequency of T cells specific for nucleoprotein (NP) and matrix protein 1 (M1) was determined by interferon-gamma (IFN-γ) ELISpot, and their phenotypic and functional properties were characterized by polychromatic flow cytometry. In a subset of M1-specific CD8(+) T cells, T cell receptor (TCR) gene expression was evaluated using an unbiased molecular approach.
  
  
  RESULTS
  Vaccination with MVA-NP+M1 was well tolerated. ELISpot responses were boosted significantly above baseline following vaccination. Increases were detected in both CD4(+) and CD8(+) T cell subsets. Clonality studies indicated that MVA-NP+M1 expanded pre-existing memory CD8(+) T cells, which displayed a predominant CD27(+)CD45RO(+)CD57(-)CCR7(-) phenotype both before and after vaccination.
  
  
  CONCLUSIONS
  MVA-NP+M1 is safe and immunogenic in older adults. Unlike seasonal influenza vaccination, the immune responses generated by MVA-NP+M1 are similar between younger and older individuals. A T cell-inducing vaccine such as MVA-NP+M1 may therefore provide a way to circumvent the immunosenescence that impairs routine influenza vaccination.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00942071.
authors.affiliation: The Jenner Institute, University of Oxford, Oxford, United Kingdom.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Antrobus
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Lillie
authors.forename: Tamara K
authors.initials: TK
authors.lastname: Berthoud
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Spencer
authors.forename: James E
authors.initials: JE
authors.lastname: McLaren
authors.forename: Kristin
authors.initials: K
authors.lastname: Ladell
authors.forename: Teresa
authors.initials: T
authors.lastname: Lambe
authors.forename: Anita
authors.initials: A
authors.lastname: Milicic
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D005260:Female; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000737:chemistry / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009698:Nucleoproteins / Q000276:immunology*; D009975:Orthomyxoviridae / Q000737:chemistry / Q000276:immunology*; D012449:Safety; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014616:Vaccinia virus / Q000737:chemistry; D014764:Viral Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000009:adverse effects* / Q000276:immunology*
chemical_list: D009698:Nucleoproteins; D014764:Viral Proteins; D014765:Viral Vaccines; D007371:Interferon-gamma