Vaccination against hepatitis C virus with dendritic cells transduced with an adenovirus encoding NS3 protein
Zabaleta A, Llopiz D, Arribillaga L, Silva L, Riezu-Boj JI, Lasarte JJ, Borrás-Cuesta F, Prieto J, Sarobe P.
Chronic infection by hepatitis C virus (HCV) is characterized by the absence of efficient antiviral T-cell responses.
Thus, vaccination strategies to induce strong anti-HCV T-cell responses are of paramount importance for prophylactic and therapeutic purposes. Dendritic cells (DCs) are the most potent antigen presenting cells; therefore, immunization with these cells loaded with viral antigens offers a new approach for induction of antiviral immunity. Here we show that immunization with DCs transfected with an adenovirus encoding non-structural 3 protein, from HCV (AdNS3), induced multiepitopic CD4 T helper cell 1 (Th1) and CD8 T-cell responses in different mouse strains. These responses prevented the growth of a tumorexpressing HCV proteins, in short- and long-term experiments.
Moreover, immunization with AdNS3-transfected DCs did not induce anti-adenoviral antibodies, as compared to direct immunization with AdNS3, but elicited T-cell responses even in the presence of pre-existing anti-adenoviral antibodies. Finally, responses induced by this protocol down-regulated the expression of HCV RNA in the liver.
In conclusion, DCs transfected with AdNS3 may prove to be an efficient anti-HCV vaccine.