Prophylactic and therapeutic vaccination with dendritic cells against hepatitis C virus infection
ABSTRACT
Antigen uptake and presentation capacities enable DC to prime and activate T cells. Recently, several studies demonstrated a diminished DC function in hepatitis C virus (HCV) infected patients showing impaired abilities to stimulate allogenic T cells and to produce IFN-gamma in HCV infected patients. Moreover, DC of patients who have resolved HCV infection behave like DC from healthy donors responding to maturation stimuli, decrease antigen uptake, up-regulate expression of appropriate surface marker, and are potent stimulators of allogenic T cells. A number of studies have demonstrated in tumour models and models of infectious diseases strong induction of immune responses after DC vaccination. Because DC are essential for T-cell activation and since viral clearance in HCV infected patients is associated with a vigorous T-cell response, we propose a new type of HCV vaccine based on ex vivo stimulated and matured DC loaded with HCV specific antigens. This vaccine circumvents the impaired DC maturation and the down regulated DC function of HCV infected patients in vivo by giving the necessary maturation stimuli and the HCV antigens in a different setting and location ex vivo. Strong humoral and cellular immune responses were detected after HCV core DC vaccination. Furthermore, DC vaccination shows partial protection in a therapeutic and prophylactic model of HCV infection. In conclusion, mice immunized with HCV core pulsed DC generated a specific antiviral response in a mouse HCV challenge model. Our results indicate that HCV core pulsed DC may serve as a new modality for immunotherapy of HCV especially in chronically infected patients.