Recombinant rabies virus as live viral vaccines for HIV-1.
Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. TuOrA288)
Pomerantz R, Foley H, Schnell M, Siler C, Dietzschold B, McGettigan J R. Pomerantz, Thomas Jefferson University, 1020 Locust St., Suite 329 JAH, Philadelphia, PA 19107, United States, Tel.: +1 215 503 85 75, Fax: +1 215 923 19 56, E-mail: roger.j.pomerantz@mail.tju.edu
To develop a live-virus strategy in the development of HIV-1 vacccines, recombinant replication-competent rabies virus (RV) vaccine strain-based vectors expressing HIV-1 envelope protein (gp160) were constructed from both a laboratory-adapted (CXCR-4-tropic) and a primary (dual-tropic) HIV-1 isolate. An additional transcription stop/start unit within the RV genome was used to express HIV-1 gp160 in addition to other RV proteins. The HIV-1 gp160 protein was stable and functionally expressed, as indicated by Western Blotting and fusion of human T-cell-lines after infection with the recombinant RV expressing the HIV-1envelope protein. Inoculation of mice with the recombinant RVs expressing HIV-1 gp160 induced a strong humoral response directed at the HIV-1 envelope protein after a single boost with recombinant HIV-1 gp120 protein. Moreover, high neutralization titers up to 1 to 800 against HIV-1 could be detected in the serum of mice primed with RV-expressing HIV-1 envelope proteins and boosted once with recombinant HIV-1 gp120. Preliminary data also indicate cross neutralization titers against other strains of HIV-1 by the same sera and high levels of specific cytotoxic T-lymphocytes (CTLs). These recombinant RVs express HIV-1 glycoproteins on the infected cells surfaces and may expose unique fusion-based epitopes. This approach has several unique characteristics which may make it an efficacious vector for a vaccine. These include low-level replication in a variety of human cell-types, altered non-pathogenic properties due to deletion of the rabies glycoprotein, lack of integration of a viral vaccine genome, and potential unique viral epitope exposure to the immune system. Of note, this report represents the first development of a non-segmented RNA virus as a HIV-1 vaccine vector. The present data indicate that a live recombinant RV, a rhabdovirus, expressing HIV-1 gp160 may serve as
Keywords: AEGIS, Rabies virus, HIV-1, AIDS Vaccines, Viral Vaccines, Virus Replication, T-Lymphocytes, Cytotoxic, Rhabdoviridae, HIV Infections, Vaccination, Human, Animal, Mice, virology 000709
TuOrA288
