Polynucleotides allowing the expression and secretion of recombinant pseudo-virus containing foreign epitopes, their production, and use

摘要

This invention provides a new approach to the design of a virus with a defective replication cycle, which can be rescued by wild type virus co-infection, and which expresses foreign antigenic epitopes that contribute to the elimination of virus infected cells and then to viral clearance. The vector of the invention, by expression of epitopes derived from common pathogens, by-passes existing tolerance of virus specific T cell responses. The vector will only replicate in virus infected cells.

主权项

1. A recombinant replication defective hepatitis B virus (HBV) comprising:
a hepatitis B virus genome defective for replication due to a deletion in the capsid-encoding portion of the virus, wherein the virus contains a polyadenylation signal for HBV mRNA, a polymerase reading frame, and a nucleotide sequence of up to about 195 nucleotides encoding at least one heterologous immuno-dominant epitope of a pathogenic bacteria or virus fused within the N-terminal part of the capsid-encoding portion of the virus between the polyadenylation signal and the start of the polymerase reading frame; wherein following infection by the virus of an isolated vertebrate hepatocyte comprising a nucleotide sequence encoding HBc for complementation of the recombinant hepatitis virus, the nucleotide sequence encoding the immuno-dominant epitope of a pathogenic bacteria or virus is expressed and the immuno-dominant epitope of a pathogenic bacteria or virus is presented at the surface of the vertebrate hepatocyte as a T cell target.