Cimetidine augments Th1/Th2 dual polarized immune responses to recombinant HBV antigens

Cimetidine (CIM) is a histamine H2 receptor inverse agonist used primarily as an anti-stomach acids drug, but recent studies showed that it may also modulate immune responses. To evaluate its potential usefulness as an adjuvant, we determined its immune modulating effects on subunit immunization using an HBV-derived recombinant protein antigen rHBsAg. CIM activated the PI3K-Akt signaling pathway in DCs. As an adjuvant, it activated immunogenic DCs, deactivated tolerogenic T cells (nTreg), and augmented both Th1- and Th2-polarlized immune responses to rHBsAg. As a result, it enhanced both antibody- and cytotoxic T cell-mediated immune responses. Importantly, in comparison with the FDA-approved human adjuvant alum, CIM is superior in its ability to block IL-10 up-regulation and potentiate Th1/Th2 dual polarization. These results suggest that CIM may be a better adjuvant for therapeutic vaccines against chronic viral infection, such as the HBV infection, where dual polarization should allow more effective elimination of infected host cells.