In vitro activation of CMV-specific human CD8+ T cells by adenylate cyclase toxoids delivering pp65 epitopes
| Authors | |
|---|---|
| Year of publication | 2012 |
| Type | Article in Periodical |
| Magazine / Source | Bone Marrow Transplantation |
| MU Faculty or unit | |
| Citation | |
| Doi | http://dx.doi.org/10.1038/bmt.2011.68 |
| Field | Oncology and hematology |
| Keywords | CMV; CD8+ T cells; CyaA toxoid; antigenic peptide epitopes |
| Description | Human CMV infects between 50-85% of healthy individuals and can cause live-threatening infections in immunocompromised patients. Therefore, peptide vaccination is being developed as a promising immunotherapeutic approach for treatment of patients at risk of CMV disease. The enzymatically inactive toxoid of Bordetella adenylate cyclase (CyaA-AC) was shown to be an efficient tool for delivery of peptide epitopes and stimulation of Ag-specific T-cell immune responses. We investigated here the capacity of two CyaA-AC constructs to deliver epitopes derived from the CMV phosphoprotein pp65 for activation of human T cells in vitro. Expansion of c-IFN-secreting CMV-specific CD8+ T cells, as well as increase of total IFN-c and TNF-a production by PBMCs from CMV-seropositive donors were observed after in vitro stimulation with CyaA-AC constructs carrying CMV epitopes, whereas limited activation of immune response occurred with free peptides. The activation of immune response was confirmed by expansion of CMV-specific T-cell clones and anti-CMV cytotoxic effect of stimulated PBMCs. These data open the way to clinical evaluation of CyaAAC constructs as tools for detection and expansion of CMV-specific T-cell immune responses for diagnostic and immunotherapeutic applications against CMV-associated diseases. |
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