Immuno-potentiating pathway of HBsAg-HBIG immunogenic complex visualized.

Chronic viral hepatitis B (CHB) is a major global health problem. A therapeutic vaccine for CHB comprised of yeast-derived recombinant HBsAg-anti-HBs immunogenic complexes (YIC) has been devloped by us. A series of clinical trials has shown its therapeutic efficacy in decreasing HBV viral load and converting serum HBeAg-positive to anti-HBe-positive status in a subpopulation of CHB patients. Herein, we present a study of the immuno-potentiating mechanisms of YIC revealed by live-cell imaging technology. We studied internalization and dissociation of YIC in cells in vitro, and antigen presentation and T cell stimulation in mice. We found that after YIC was internalized via the Fcγ receptors (FcγR) of antigen presenting cells, it was subsequently transferred through early and late endosomal into lysosomal compartments. The dissociation of YIC was mainly observed in the late endosome. Furthermore when YIC were injected into mice, the populations of IFN-γ- and TNF-α-producing CD8+ and CD4+ T cells were higher in the YIC group than in controls receiving antigen or antibody alone. These observations supplement the known mechanisms of YIC action as a therapeutic vaccine for CHB.