CHIMERIC HEPATITIS-B CORE ANTIGEN PARTICLES CONTAINING B-EPITOPES AND TH-EPITOPES OF HUMAN PAPILLOMAVIRUS TYPE-16 E7 PROTEIN INDUCE SPECIFIC ANTIBODY AND T-HELPER RESPONSES IN IMMUNIZED MICE

The use of hepatitis B core antigen (HBcAg) as an immunogenic delivery vehicle for foreign epitopes has been reported. Here we report the insertion of DNA sequences encoding immunodominant linear B-epitopes and a ''universal'' T-helper epitope of human papillomavirus (HPV) type 16 E7 transforming protein into the full-length HBcAg gene cloned into an inducible bacterial expression plasmid (pPN1.0). The resulting chimeric proteins assembled into particles which were highly immunogenic. Mice immunised with particles containing one or two of the three E7 B-epitopes under consideration produced strong epitope-specific antibody responses with both IgG and IgG2a components which recognised eukaryotic E7. T-proliferative responses were elicited to the E7 T-epitope as well as HBcAg T-epitope(s). Lymph node cells from immunised mice produced IL-2 and IL-4 when specifically recalled in vitro, indicating stimulation of both Th, and Th, helper cell compartments. Since HBcAg particles can be administered in adjuvant acceptable for human application and can elicit mucosal responses after nasal or oral immunisation, these results have implications for vaccine design in HPV16-associated anogenital cancer. (C) 1994 Academic Press, Inc.