A Recombinant Modified Vaccinia Ankara Vaccine Encoding Epstein-Barr Virus (EBV) Target Antigens: A Phase I Trial in UK Patients with EBV-Positive Cancer Academic Article uri icon

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abstract

  • PURPOSE: Epstein-Barr virus (EBV) is associated with several cancers in which the tumor cells express EBV antigens EBNA1 and LMP2. A therapeutic vaccine comprising a recombinant vaccinia virus, MVA-EL, was designed to boost immunity to these tumor antigens. A phase I trial was conducted to demonstrate the safety and immunogenicity of MVA-EL across a range of doses. EXPERIMENTAL DESIGN: Sixteen patients in the United Kingdom (UK) with EBV-positive nasopharyngeal carcinoma (NPC) received three intradermal vaccinations of MVA-EL at 3-weekly intervals at dose levels between 5 × 10(7) and 5 × 10(8) plaque-forming units (pfu). Blood samples were taken at screening, after each vaccine cycle, and during the post-vaccination period. T-cell responses were measured using IFNγ ELISpot assays with overlapping EBNA1/LMP2 peptide mixes or HLA-matched epitope peptides. Polychromatic flow cytometry was used to characterize functionally responsive T-cell populations. RESULTS: Vaccination was generally well tolerated. Immunity increased after vaccination to at least one antigen in 8 of 14 patients (7/14, EBNA1; 6/14, LMP2), including recognition of epitopes that vary between EBV strains associated with different ethnic groups. Immunophenotypic analysis revealed that vaccination induced differentiation and functional diversification of responsive T-cell populations specific for EBNA1 and LMP2 within the CD4 and CD8 compartments, respectively. CONCLUSIONS: MVA-EL is safe and immunogenic across diverse ethnicities and thus suitable for use in trials against different EBV-positive cancers globally as well as in South-East Asia where NPC is most common. The highest dose (5 × 10(8) pfu) is recommended for investigation in current phase IB and II trials.

authors

  • Price, David
  • Taylor, GS
  • Jia, H
  • Harrington, K
  • Lee, LW
  • Turner, J
  • Ladell, K
  • Price, DA
  • Tanday, M
  • Matthews, J
  • Roberts, C
  • Edwards, C
  • McGuigan, L
  • Hartley, A
  • Wilson, S
  • Hui, EP
  • Chan, ATC
  • Rickinson, AB
  • Steven, NM

publication date

  • October 1, 2014

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