Multiepitopic HLA-A*0201-restricted immune response against hepatitis B surface antigen after DNA-based immunization

CTL together with anti-envelope Abs represent major effecters for viral cle arance during hepatitis B virus (HBV) infection. The induction of strong cy totoxic and Ab responses against the envelope proteins after DNA-based immu nization has been proposed as a promising therapeutic approach to mediate v iral clearance in chronically infected patients. Here, we studied the CTL r esponses against previously described hepatitis B surface Ag (HBsAg)-HLA-A* 0201-restricted epitopes after DNA-based immunization in HLA-A*0201 transge nic mice. The animal model used was Human Human D-b (HHD) mice, which are d eficient for mouse MHC class I molecules (beta(2)-microglobulin(-/-) Db-/-) and transgenic for a chimeric HLA-A*0201/D-b molecule covalently bound to the human beta(2)-microglobulin (HHD+/+), Immunization of these mice with a DNA vector encoding the small and the middle HBV envelope proteins carryin g HBsAg induced CTL responses against several epitopes in each animal, This study performed on a large number; of animals described dominant epitopes with specific CTL induced in all animals and others,vith a weaker frequency of recognition. These results confirmed the relevance of the HHD transgeni c mouse model in the assessment of vaccine constructs for human use. Moreov er, genetic immunization of HLA-A2 transgenic mice generates IFN-gamma-secr eting CD8(+) T lymphocytes specific for endogenously processed peptides and with recognition specificities similar to those described during self-limi ted infection in humans. This suggests that responses induced by DNA immuni zation could have the same immune potential as those developing during natu ral HBV infection in human patients.