Characterizing the cellular immune response to parainfluenza virus 3

Paibel I. Aguayo-Hiraldo, Reuben J. Arasaratnam, Ifigeneia Tzannou, Manik Kuvalekar, Premal Lulla, Swati Naik, Caridad A. Martinez, Pedro A. Piedra, Juan F. Vera, Ann M. Leen

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)153-161
Number of pages9
JournalJournal of Infectious Diseases
Volume216
Issue number2
DOIs
StatePublished - Jul 15 2017

Keywords

  • Immunotherapy
  • Parainfluenza virus 3
  • Virus-specific T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Characterizing the cellular immune response to parainfluenza virus 3'. Together they form a unique fingerprint.

  • Cite this

    Aguayo-Hiraldo, P. I., Arasaratnam, R. J., Tzannou, I., Kuvalekar, M., Lulla, P., Naik, S., Martinez, C. A., Piedra, P. A., Vera, J. F., & Leen, A. M. (2017). Characterizing the cellular immune response to parainfluenza virus 3. Journal of Infectious Diseases, 216(2), 153-161. https://doi.org/10.1093/infdis/jix203