As disclosed herein, the preS antigen on infectious hepatitis B virus (HBV) particles can provide B and T ceil epitopes that promote the humoral and cellular responses and enhance the seroprotection rate by overcoming non-responsiveness to the S antigen-only vaccines. Therefore, compositions and methods are disclosed using the preS antigen to develop vaccines and immune therapies for treating or preventing hepatitis B infection, in particular, virus-like particles (VLPs) are disclosed that contain the preS antigen on its surface. These VLPs can be used alone or in combination with vaccines containing the hepatitis B surface antigen (HBsAg) to vaccinate subjects against HBV as well as to activate T ceils for adoptive T cell therapy to eradicate HBV infected hapatocytes.
