RECOMBINANT RHABDOVIRUSES AS LIVE-VIRAL VACCINES FOR IMMUNODEFICIENCY VIRUSES

摘要

This invention provides recombinant, replication-competent Rhabdovirus vaccine strain-based expression vectors for expressing heterologous viral antigenic polypeptides such as immunodeficiency virus envelope proteins or subparts thereof. An additional transcription stop/start unit within the Rhabdovirus genome is inserted to express the heterologouos antigenic polypeptides. The HIV-1 gp 160 protein is stably and functionally expressed, as indicated by fusion of human T cell-lines after infection with the recombinant RVs. Inoculation of mice with the recombinant Rabies viruses expressing HIV-1 gp160 induces a strong humoral response directed against the HIV-1 envelope protein after a single boost with an isolated recombinant HIV-1 gp120 protein. Moreover, high neutralization titers, Up to 1:800, against HIV-1 are detected in the mouse sera. The present invention also shows that a single vaccination with recombinant RV expressing HIV-1 envelope protein elicits a strong, long-lasting CTL response specific against HIV-1 proteins, such as the envelope protein of different HIV-1 strains. These recombinant viral vectors expressing viral antigenic polypeptides provide useful and effective pharmaceutical compositions for the generation of viral specific immune responses.