Publication

T-Cell Therapeutics Targeting Human Parainfluenza Virus 3 Are Broadly Epitope Specific and Are Cross Reactive With Human Parainfluenza Virus 1

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Last modified
  • 06/25/2025
Type of Material
Authors
    Katherine M. Harris, Children’s National HospitalSarah E. Horn, Children’s National HospitalMelanie Grant, Emory UniversityHalli Lang, Children’s National HospitalGelina Sani, Children’s National HospitalMariah A. Jensen-Wachspress, Children’s National HospitalVaishnavi V. Kankate, Children’s National HospitalAnushree Datar, Children’s National HospitalChristopher A. Lazarski, Children’s National HospitalCatherine M. Bollard, Children’s National HospitalMichael D. Keller, Children’s National Hospital
Language
  • English
Date
  • 2020-10-05
Publisher
  • Frontiers
Publication Version
Copyright Statement
  • © 2020 Harris, Horn, Grant, Lang, Sani, Jensen-Wachspress, Kankate, Datar, Lazarski, Bollard and Keller
License
Final Published Version (URL)
Title of Journal or Parent Work
Volume
  • 11
Start Page
  • 575977
End Page
  • 575977
Grant/Funding Information
  • This work was supported by grants from the National Institutes of Health (K23-HL136783-01 to MK), the Jeffrey Modell Foundation, and the Board of Visitors of the Children’s National Health System.
Supplemental Material (URL)
Abstract
  • Human Parainfluenza Virus-3 (HPIV3) causes severe respiratory illness in immunocompromised patients and lacks approved anti-viral therapies. A phase I study of adoptively transferred virus-specific T-cells (VSTs) targeting HPIV3 following bone marrow transplantation is underway (NCT03180216). We sought to identify immunodominant epitopes within HPIV3 Matrix protein and their cross-reactivity against related viral proteins. VSTs were generated from peripheral blood of healthy donors by ex-vivo expansion after stimulation with a 15-mer peptide library encompassing HPIV3 matrix protein. Epitope mapping was performed using IFN-γ ELIspot with combinatorial peptide pools. Flow cytometry was used to characterize products with intracellular cytokine staining. In 10 VST products tested, we discovered 12 novel immunodominant epitopes. All products recognized an epitope at the C-terminus. On IFN-γ ELISpot, individual peptides eliciting activity demonstrated mean IFN-γ spot forming units per well (SFU)/1x105 cells of 115.5 (range 24.5–247.5). VST products were polyfunctional, releasing IFN-γ and TNF-α in response to identified epitopes, which were primarily HLA Class II restricted. Peptides from Human Parainfluenza Virus-1 corresponding to the HPIV3 epitopes showed cross-reactivity for HPIV1 in 11 of 12 tested epitopes (mean cross reactivity index: 1.19). Characterization of HPIV3 epitopes may enable development of third-party VSTs to treat immune suppressed patients with HPIV infection.
Author Notes
Keywords
Research Categories
  • Health Sciences, Immunology
  • Health Sciences, Pathology
  • Biology, Cell

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