In addition to the relief of immune tolerance, NA may suppress the HBsAg production from free virus, but no effect is expected for those HBsAg produced by integrated HBV genome. These two types of HBsAg may have some differences on protein conformation and behavior (46,47). The vaccine is produced according to free virus. Therefore, when the HBsAg produced by free virus is suppressed by NA to a low level, the vaccine may be recognized as a new antigen. The immune response elicited by the therapeutic vaccine may have a potential on suppression of free virus.