Journal article
Generation of Norovirus-Specific T cells from Human Donors with extensive Cross-Reactivity to variant sequences: implications for Immunotherapy
The Journal of Infectious Diseases, Vol.221(4), pp.578-588
2019
Abstract
Background
Chronic norovirus infection in immunocompromised patients can be severe, and presently there is no effective treatment. Adoptive transfer of virus-specific T cells has proven to be safe and effective for the treatment of many viral infections, and this could represent a novel treatment approach for chronic norovirus infection. Hence, we sought to generate human norovirus-specific T cells (NSTs) that can recognize different viral sequences.
Methods
Norovirus-specific T cells were generated from peripheral blood of healthy donors by stimulation with overlapping peptide libraries spanning the entire coding sequence of the norovirus genome.
Results
We successfully generated T cells targeting multiple norovirus antigens with a mean 4.2 ± 0.5-fold expansion after 10 days. Norovirus-specific T cells comprised both CD4+ and CD8+ T cells that expressed markers for central memory and effector memory phenotype with minimal expression of coinhibitory molecules, and they were polyfunctional based on cytokine production. We identified novel CD4- and CD8-restricted immunodominant epitopes within NS6 and VP1 antigens. Furthermore, NSTs showed a high degree of cross-reactivity to multiple variant epitopes from clinical isolates.
Conclusions
Our findings identify immunodominant human norovirus T-cell epitopes and demonstrate that it is feasible to generate potent NSTs from third-party donors for use in antiviral immunotherapy.
Details
- Title
- Generation of Norovirus-Specific T cells from Human Donors with extensive Cross-Reactivity to variant sequences: implications for Immunotherapy
- Authors/Creators
- R. Hanajiri (Author/Creator) - Children’s National Health SystemG.M. Sani (Author/Creator) - Children’s National Health SystemD. Saunders (Author/Creator) - Children’s National Health SystemP.J. Hanley (Author/Creator) - Children’s National Health SystemA. Chopra (Author/Creator) - Vanderbilt UniversityS.A. Mallal (Author/Creator) - Vanderbilt UniversityS.V. Sosnovtsev (Author/Creator) - National Institute of Allergy and Infectious DiseasesJ.I. Cohen (Author/Creator) - National Institute of Allergy and Infectious DiseasesK.Y. Green (Author/Creator) - National Institute of Allergy and Infectious DiseasesC.M. Bollard (Author/Creator) - Children’s National Health SystemM.D. Keller (Author/Creator) - Children’s National Health System
- Publication Details
- The Journal of Infectious Diseases, Vol.221(4), pp.578-588
- Publisher
- Oxford University Press
- Identifiers
- 991005540909007891
- Copyright
- © 2019 The Author(s).
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.246 Diarrheal Diseases
- 1.246.710 Enteric Viruses
- Web Of Science research areas
- Immunology
- Infectious Diseases
- Microbiology
- ESI research areas
- Immunology