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Recombinant Rabies Virus as Potential Live-Viral Vaccines for HIV-1 M. J. SCHNELL*1‚2, H. D. FOLEY1‚3, C. A. SILER1‚2, B. DIETZSCHOLD3, J. P. MCGETTIGAN1‚2‚4, and R. J. POMERANTZ1‚2‚4. The Dorance H. Hamilton Labs., 1Ctr. for Human Virology; 2Dept. of Biochemistry and Molecular Pharmacology; 3Microbiology and Immunology; and 4Med Recombinant, replication competent rabies virus (RV) vaccine strain-based vectors expressing human immunodeficiency virus type 1 (HIV-1) envelope protein (gp160) were constructed from both a laboratory adapted (CXCR4-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 the other RV proteins. The HIV-1 gp160 protein was stably and functionally expressed, as indicated by Western blotting and fusion of human T cell-lines after infection with the recombinant RVs expressing HIV-1 envelope protein. Inoculation of mice with the recombinant RVs expressing HIV-1 gp160 induced a strong humoral response directed against the HIV-1 envelope protein after a single boost with recombinant HIV-1 gp120 protein. Moreover, high neutralization titers up to 1:800 against HIV-1 could be detected in the sera of mice primed with RV expressing HIV-1NL4–3 envelope protein and with recombinant HIV-1 gp120, and preliminary data indicate cross-neutralization titers against HIV-189.6 by the same sera. These recombinant RV express HIV-1 glycoproteins on the infected cell surfaces, and may expose unique fusion-based epitopes. These data indicate that a live recombinant RV, a rhabdovirus, expressing HIV-1 gp160 may serve as an effective vector for an HIV-1 vaccine. Key Words: envelope, rhabdovirus, vaccine |
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© 7th
Conference on Retroviruses and Opportunistic Infections, |