RECOMBINANT HBSAG VIRUS-LIKE PARTICLES CONTAINING POLYEPITOPES OF INTEREST, THEIR PRODUCTION AND USE

摘要

The hepatitis B surface antigen (HBsAg) can assemble into sub-virion virus like particles (VLPs). By fusing immunogenic peptides to the amino-terminus of HBsAg, several bivalent vaccines have been developed. In one example, an optimized HIV-1 polyepitope-HBsAg recombinant protein assembled into VLPs and was efficiently secreted. DNA immunization in mice resulted in the induction of humoral neutralising response against the carrier and enhanced levels of HIV- 1 specific CD8+ T lymphocytes activation. In an onther example, the successful expression of novel recombinant HIV-1/HBV virus-like particles (VLPs) in Nicotiana tabacum and Arabidopsis thaliana is decribed. The production levels and quality of the recombinant VLPs were comparable in the two plants, showing that parameters intrinsic to the recombinant proteins determined their assembly into VLPs. Theses recombinant transgenes represent an innovative tool to set up a bivalent anti-H IV- 1 /-HBV vaccine based on oral administration of crude extracts from transgenic plants. In a final example, it is demonstrated that by oral administration of transgenic plant crude extracts to humanized HSB mice it is possible to induce the activation of anti-HIV-1 specific CD8+ T cells in peripheral lymph nodes and spleen.