In vitro activation of CMV-specific human CD8(+) T cells by adenylate cyclase toxoids delivering pp65 epitopes.
Bone Marrow Transplant
; 47(2): 243-50, 2012 Feb.
Article
em En
| MEDLINE
| ID: mdl-21441962
ABSTRACT
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 γ-IFN-secreting CMV-specific CD8(+) T cells, as well as increase of total IFN-γ and TNF-α 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 CyaA-AC(-) constructs as tools for detection and expansion of CMV-specific T-cell immune responses for diagnostic and immunotherapeutic applications against CMV-associated diseases.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
/
Adenilil Ciclases
/
Proteínas da Matriz Viral
/
Linfócitos T CD8-Positivos
/
Epitopos de Linfócito T
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Vacinas contra Citomegalovirus
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Citomegalovirus
Limite:
Humans
Idioma:
En
Revista:
Bone Marrow Transplant
Assunto da revista:
TRANSPLANTE
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
República Tcheca