Publication details

In vitro activation of CMV-specific human CD8+ T cells by adenylate cyclase toxoids delivering pp65 epitopes

Authors

JELÍNEK Jiří ADKINS Irena MIKULKOVA Z. JAGOSOVA J. PACASOVA R. MICHLICKOVA S. SEBO P. MICHÁLEK Jaroslav

Year of publication 2012
Type Article in Periodical
Magazine / Source Bone Marrow Transplantation
MU Faculty or unit

Faculty of Medicine

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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