Characterizing the Cellular Immune Response to Parainfluenza Virus 3

J Infect Dis. 2017 Jul 15;216(2):153-161. doi: 10.1093/infdis/jix203.


Parainfluenza virus type 3 (PIV3) infections are a major cause of morbidity and mortality in immunocompromised individuals, with no approved therapies. Our group has demonstrated the safety and efficacy of adoptively transferred virus-specific T cells for the prevention and treatment of a broad range of viral infections including BK virus, cytomegalovirus, adenovirus, human herpesvirus 6, and Epstein-Barr virus. However, this approach is restricted to well-characterized viruses with known immunogenic/protective T-cell target antigens, precluding extension to PIV3. We now characterize the cellular immune response to all 7 PIV3-encoded antigens in 17 healthy donors and define a hierarchy of immunogenicity based on the frequency of responding donors and the magnitude of specific cells. We show that reactive populations of both CD4+ and CD8+ T cells are capable of producing Th1-polarized effector cytokines and killing PIV3-expressing targets. Furthermore, we confirm the clinical relevance of these cells by demonstrating a direct correlation between the presence of PIV3-specific T cells and viral control in allogeneic hematopoietic stem cell transplant recipients. Taken together, our findings support the clinical use of PIV3-specific T cells produced with our Good Manufacturing Practice-compliant manufacturing process, in immunocompromised patients with uncontrolled infections.

Keywords: Parainfluenza virus 3; immunotherapy; virus-specific T cells.

Publication types

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

MeSH terms

  • Antigens, Viral / immunology*
  • Child, Preschool
  • Cytokines / immunology
  • Female
  • Humans
  • Immunity, Cellular*
  • Immunotherapy
  • Infant
  • Leukocytes, Mononuclear / virology*
  • Male
  • Middle Aged
  • Parainfluenza Virus 3, Human*
  • Respirovirus Infections / immunology*
  • T-Lymphocytes / immunology*


  • Antigens, Viral
  • Cytokines