BK Polyomavirus–Specific CD8 T-Cell Expansion In Vitro Using 27mer Peptide Antigens for Developing Adoptive T-Cell Transfer and Vaccination. (28th August 2020)

• Record Type: Journal Article
• Authors: Wilhelm, Maud; Kaur, Amandeep; Wernli, Marion; Hirsch, Hans H
• Is Part Of: Journal of infectious diseases. Volume 223:Number 8(2021)
• Page Start: 1410
• Page End: 1422
• Publication Date: 2020-08-28
• Subjects: BK virus -- polyoma -- T cells -- peptides -- antigen-presenting cells -- vaccine; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiaa546
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Background: BK polyomavirus (BKPyV) remains a significant cause of premature kidney transplant failure. In the absence of effective antivirals, current treatments rely on reducing immunosuppression to regain immune control over BKPyV replication. Increasing BKPyV-specific CD8 T cells correlate with clearance of BKPyV DNAemia in kidney transplant patients. We characterized a novel approach for expanding BKPyV-specific CD8 T cells in vitro using 27mer-long synthetic BKPyV peptides, different types of antigen-presenting cells, and CD4 T cells. Methods: Langerhans cells and immature or mature monocyte-derived dendritic cells (Mo-DCs) were generated from peripheral blood mononuclear cells of healthy blood donors, pulsed with synthetic peptide pools consisting of 36 overlapping 27mers (27mP) or 180 15mers (15mP). BKPyV-specific CD8 T-cell responses were assessed by cytokine release assays using 15mP or immunodominant 9mers. Results: BKPyV-specific CD8 T cells expanded using 27mP and required mature Mo-DCs ( P = .0312) and CD4 T cells ( P = .0156) for highest responses. The resulting BKPyV-specific CD8 T cells proliferated, secreted multiple cytokines including interferon γ and tumor necrosis factor α, and were functional (CD107a + /PD1 – ) and cytotoxic. Conclusions: Synthetic 27mP permit expanding BKPyV-specific CD8 T-cell responses when pulsing mature Mo-DCs in presence of CD4 T cells, suggesting novel and safe approaches to vaccination and adoptive T-cell therapies for patients before and after kidney transplantation. Abstract : To develop novel and safe approaches to vaccination and T-cell therapies targeting BK polyomavirus after transplantation, we characterized BKPyV-specific CD8 T-cell responses expanding in vitro expanding after pulsing mature monocyte-derived dendritic cells with 27mer-peptides in presence of CD4 T-cells