The Use of Hepatitis B Surface Antigen-Small as a Vaccine System for Delivery of Foreign CTL Epitopes

The small envelope of hepatitis B virus (HBV) can self-assembles into virus-like particles (VLPs) and they are highly immunogenic. The use of hepatitis B surface antigen (HBsAg) as a vector to deliver foreign CTL epitopes has met with little success due to the constraints of HBsAg stability and secretion imposed by the insertion of foreign sequence into critical regions. In this study, the efficacy of the small HBsAg envelope protein to deliver foreign CTL epitopes using a protective CTL epitope of human respiratory syncytial virus (RSV) was investigated. The strategy of deleting a DNA sequence encoding HBsAg-specific CTL epitopes at different sites and replacing with DNA sequence encoding RSV CTL epitope resulted in recombinant HBsAg DNA immunogens which elicited effector and memory CTL responses in vitro, and RSV protective responses in vivo when these recombinant HBsAg DNAs were used to immunised mice. These data demonstrate the efficacy of HBsAg DNA as a vector for the delivery of disease relevant protective CTL responses. They also suggest the applicability of the approach to derive recombinant HBsAg DNA immunogens simultaneously encoding protective CTL epitopes for multiple diseases. The use of HBsAg VLPs has been used globally as administered vaccine for hepatitis B virus infection makes it an attractive vector candidate to deliver immunogens for other diseases. Since the HBsAg DNAs we tested formed recombinant HBsAg VLPs, our results have implications for the development of vaccination strategies using either recombinant HBsAg DNA or VLP vaccines.