Since HIS mice contained broad naïve B cell repertoires, we analyzed the induction of human antigen-specific B cell responses after immunization with commercially available human vaccines. We designed a vaccination protocol based on repeated intramuscular immunizations (3 injections with 2-week intervals) of 10-14-week old HIS mice with vaccines containing hepatitis B surface antigen (HBsAg) or TT. Seven days after the last immunization mice were sacrificed, the blood and the lymphoid organs were harvested, and the phenotype and function of human cells was analyzed.