34 Regulating the viral load using antiviral drugs may help control the balance between the cytotoxic and inflammatory effects of virus-specific T cells. Interestingly, specific T cell responses might even be restored in this setting.35 In addition, a reduction of HBeAg load could be observed upon antiviral treatments in some patients,36 and HBs seroconversion BYL719 order has been achieved following mDC-based vaccine.32 This is important, as we showed here that HBeAg status is critical for successful immunostimulation in chronic HBV patients. The vast majority of HBeAg-negative

patients treated with new analogs (entecavir and tenofovir) have undetectable HBV DNA, but have nearly no chance to achieve HBs antigen clearance. These patients, who need to be treated throughout their lives, would be the ideal target for the pDC-based immunotherapy in the future. The advantage of pDCs over mDCs in eliciting immune responses was clearly demonstrated in our previous work,27, 28 where we directly compared the two cell types and their capacity to elicit immune responses to a variety of tumor and viral antigens. Furthermore, in contrast with autologous mDCs that required patients’ cells,

the pDC strategy could be directly applied to all HLA-A*0201+ patients. These settings have check details already been shown to be safe in chronic HBV patients.11, 32 Our previous work clearly demonstrates that the pDC strategy generates potent HLA-A0201-restricted antigen-specific cytotoxic T cells without cross-reactivity to different HLA alleles and without bystander alloreactivity.27, 28 Mutations within HBV antigens have been shown to occur during the progression of HBV infection.37 However, it appears that T cell escape mutants are not common in chronic HBV patients, as an intact core 18-27 epitope has been described in more than 92% of chronic HBV patients.38 In addition, CTLs specific

for the wild-type MCE HBc18-27 epitope could still recognize target cells presenting a mutated HBc18-27 epitope,37 therefore limiting the complete ineffectiveness of such an immunotherapy. As mutations occur in limited positions, mutated epitopes could also be used to load the pDCs to trigger CTLs toward the mutated epitopes. We developed a new Hepato-HuPBL mouse model consisting in humanized mice engrafted with HBV-antigen expressing hepatocytes. Indeed, the existing chimeric and transgenic models are not suitable for testing such immunotherapies that required both the context of a human immune system and HBV antigen-expressing human hepatocytes. The human liver-uPA-SCID model further infected with HBV39 is devoid of immune cells, the HBV transgenic mouse40 is restricted to a murine context, and HLA-A2 transgenic mice13 allow epitope discovery but not therapeutic testing.