The long term goal of this project is to develop recombinants of the enveloped virus, vesicular stomatitis virus (VSV), as an HIV vaccine. This laboratory has developed a system for obtaining recombinants of this negative-strand RNA virus that express either the HIV-1 envelope protein or a hybrid protein consisting of the extracellular and transmembrane domains of the HIV-1 envelope linked to the cytoplasmic domain of the VSV glycoprotein (G). Several important features of the recombinant VSV system make it useful for vaccine development: VSV recombinants can be grown to extremely high titers, the recombinants are genetically stable and express large amounts of the foreign protein with only five other viral proteins, the HIV/G hybrid protein is incorporated into the virus particle, and the recombinants can be tested for antigenicity in a small animal model. VSV causes a non-lethal, self-limiting disease in livestock, but it causes only a mild, flu-like illness in humans. It may therefore be possible to use attenuated, live VSV/HIV recombinants directly as human vaccines. Replication-defective or killed VSV/HIV recombinants could also be used as a completely safe alternative. The immediate goals of this optimize incorporation of a recombinant HIV-1 envelope into VSV/HIV particles in the absence of the VSV envelope protein, to construct VSV/HIV recombinants expressing the envelope of a primary HIV-1 isolate, to generate defective HIV/VSV recombinants that are capable of only one round of infection, and to test the live, defective, or killed VSV/HIV recombinants for their ability to induce HIV-1 neutralizing antibodies in mice.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Special Emphasis Panel (ZRG5-AAR (03))
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Yale University
Schools of Medicine
New Haven
United States
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Schell, John B; Bahl, Kapil; Folta-Stogniew, Ewa et al. (2015) Antigenic requirement for Gag in a vaccine that protects against high-dose mucosal challenge with simian immunodeficiency virus. Virology 476:405-12
Schell, John B; Bahl, Kapil; Rose, Nina F et al. (2012) Viral vectored granulocyte-macrophage colony stimulating factor inhibits vaccine protection in an SIV challenge model: protection correlates with neutralizing antibody. Vaccine 30:4233-9
Schell, John B; Rose, Nina F; Bahl, Kapil et al. (2011) Significant protection against high-dose simian immunodeficiency virus challenge conferred by a new prime-boost vaccine regimen. J Virol 85:5764-72
Schlehuber, Lisa D; Rose, John K (2004) Prediction and identification of a permissive epitope insertion site in the vesicular stomatitis virus glycoprotein. J Virol 78:5079-87
Ramsburg, Elizabeth; Rose, Nina F; Marx, Preston A et al. (2004) Highly effective control of an AIDS virus challenge in macaques by using vesicular stomatitis virus and modified vaccinia virus Ankara vaccine vectors in a single-boost protocol. J Virol 78:3930-40
Publicover, Jean; Ramsburg, Elizabeth; Rose, John K (2004) Characterization of nonpathogenic, live, viral vaccine vectors inducing potent cellular immune responses. J Virol 78:9317-24
Quinones-Kochs, Miriam I; Buonocore, Linda; Rose, John K (2002) Role of N-linked glycans in a human immunodeficiency virus envelope glycoprotein: effects on protein function and the neutralizing antibody response. J Virol 76:4199-211
Haglund, Karl; Leiner, Ingrid; Kerksiek, Kristen et al. (2002) High-level primary CD8(+) T-cell response to human immunodeficiency virus type 1 gag and env generated by vaccination with recombinant vesicular stomatitis viruses. J Virol 76:2730-8
Haglund, Karl; Leiner, Ingrid; Kerksiek, Kristen et al. (2002) Robust recall and long-term memory T-cell responses induced by prime-boost regimens with heterologous live viral vectors expressing human immunodeficiency virus type 1 Gag and Env proteins. J Virol 76:7506-17
Rose, N F; Marx, P A; Luckay, A et al. (2001) An effective AIDS vaccine based on live attenuated vesicular stomatitis virus recombinants. Cell 106:539-49

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