Immunologic Profiling of Human Metapneumovirus for the Development of Targeted Immunotherapy

J Infect Dis. 2017 Sep 15;216(6):678-687. doi: 10.1093/infdis/jix358.


Human metapneumovirus (hMPV) is a respiratory virus detected in ≥9% of allogeneic hematopoietic stem cell transplant (HSCT) recipients, in whom it can cause significant morbidity and mortality. Given the lack of effective antivirals, we investigated the potential for immunotherapeutic intervention, using adoptively transferred T cells. Thus, we characterized the cellular immune response to the virus and identified F, N, M2-1, M, and P as immunodominant target antigens. Reactive T cells were polyclonal (ie, they expressed CD4 and CD8), T-helper type 1 polarized, and polyfunctional (ie, they produced interferon γ, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, and granzyme B), and they were able to kill autologous antigen-loaded targets. The detection of hMPV-specific T cells in HSCT recipients who endogenously controlled active infections support the clinical importance of T-cell immunity in mediating protective antiviral effects. Our results demonstrate the feasibility of developing an immunotherapy for immunocompromised patients with uncontrolled infections.

Keywords: Human metapneumovirus; immunotherapy; virus-specific T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Feasibility Studies
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Granzymes / immunology
  • Humans
  • Immunity, Cellular
  • Immunocompromised Host / immunology
  • Immunodominant Epitopes / immunology
  • Immunotherapy, Adoptive*
  • Interferon-gamma / immunology
  • Leukocytes, Mononuclear / virology
  • Male
  • Metapneumovirus / immunology*
  • Metapneumovirus / isolation & purification
  • Middle Aged
  • Paramyxoviridae Infections / immunology
  • Paramyxoviridae Infections / therapy*
  • T-Lymphocytes / virology
  • Tumor Necrosis Factor-alpha / immunology
  • Young Adult


  • Immunodominant Epitopes
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Granzymes