All HIS mice showed human reconstitution (.20% hCD45 + cells) in the blood before starting the immunization protocol, which correlated with human engraftment in lymphoid organs. Overall, 42% of HBsAg-vaccinated (8 out of 19 vaccinated animals) and 40% of TT-vaccinated (6 out of 15) HIS mice showed significant production of antigen-specific IgM antibodies, as detected by ELISA (Figure 2A) . We performed a kinetic monitoring of antigen-specific plasma Ig levels in individual HBsAg-vaccinated responder HIS mice and we observed that after the first immunization antigen-specific Igs were rarely detected. In contrast, after the second immunization antigen-specific IgM was detected, which steadily increased after the third immunization with approximately 25-40% of responder mice also showing an antigen-specific IgG response (Figure 2A) . This suggests that repeated vaccination leads to enhanced antigen-specific antibody production. The responder mice exhibited higher total IgM (173641 mg/ml) and total IgG (4596140 mg/ml) concentrations in their plasma, as compared to PBS-injected (IgM: 37612 mg/ml; IgG: 191658 mg/ml) and non-responder vaccinated (IgM: 44611 mg/ml; IgG: 192667 mg/ml) animals ( Figure 2B) .