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Member Information
Stuart Isaacs, MD
Associate Professor of Medicine, Division of Infectious Diseases
Office Phone: 215-662-2150
Office Fax: 215-349-5111
Email: Isaacs@mail.med.upenn.edu
Website(s): http://www.uphs.upenn.edu/idd/16.html
Education: MD 1985, Yale University School of Medicine
Keywords: vaccinia virus, recombinant vaccines, immune responses, HIV-1 Gag
Research and/or Clinical Interests:
We are developing recombinant vaccinia viruses that present foreign antigens in a novel fashion that may result in enhanced immunity
Summary:
Therapeutic and preventative vaccines against HIV are desperately needed for the potential eradication of HIV in infected patients and for the prevention of acquisition of HIV disease. The development of recombinant poxvirus-based HIV vaccines have shown promise. However, many feel that the current generation of vaccines will not prove to be effective. To date, the majority of poxvirus-based HIV vaccines produce HIV antigens that either remain in the cytoplasm or are secreted from infected cells, or are expressed on the outer membrane. We are investigating a novel approach for the presentation of HIV antigens using a poxvirus vector. We have developed a strategy to display foreign proteins on a vaccinia virion. It is our hypothesis that HIV antigens presented on the outer surface of a vaccinia virion will generate enhanced immunity.
Representative Publications:
Isaacs, S.N., Yi, Y., Singh A., Collman, R.G., A macrophage fusion assay for rapid screening of cloned HIV-1 Env using dual recombinant vaccinia viruses expressing distinct RNA polymerases. Journal of Virological Methods, 81: 55-61 (1999).
Yi, Y., Isaacs, S.N., Williams, D.A., Frank, I., Schols, D., DeClercq, E., Kolson, D.L., Collman, R.G., Role of CXCR4 in Cell-Cell Fusion and Infection of Monocyte-Derived Macrophages by Primary Human Immunodeficiency Virus Type 1 Strains: Two Distinct Mechanisms of HIV-1 Dual Tropism. Journal of Virology 73: 7117-7125 (1999).
Weissman, D., Ni, H., Scales, D., Dude, A., Capodici, J., McGibney, K., Abdool, A., Isaacs, S.N., Cannon, G., Karikó, K. HIV gag mRNA transfection of dendritic cells (DC) delivers encoded antigen to MHC class I and II molecules, causes DC maturation, and induces a potent human in vitro primary immune response. Journal of Immunology, 165: 4710-4717 (2000)
Yi, Y., Singh, A., Isaacs, S.N., Collman, R.G., A CCR5/CXCR4-independent coreceptor pathway on human macrophages supports efficient SIV Env-mediated fusion but not infection: Implications for alternative pathways of viral entry. Virology 284: 142-151 (2001).
Singh, A., Yi, Y., Isaacs, S.N., Kolson, D.L., Collman, R.G. Concordant utilization of macrophage entry coreceptors by related variants within an HIV-1 primary isolate viral swarm. AIDS Research Human Retroviruses 17:957-963 (2001).
Lamikanra, A., Pan, Z-K., Isaacs, S.N., Wu, T.-C., Paterson, Y. The ability to induce the regression of established HPV-16 immortalized tumors in vivo by vaccinia viruses expressing different forms of HPV-16 E7 correlates with enhanced CD8+ T cell responses that home to the tumor site. Journal of Virology 75:9654-9664 (2001).
Isaacs, S.N., Critical evaluation of smallpox vaccination for laboratory workers: an alternative view. Occupational & Environmental Medicine 59:573-574 (2002)
Amorosa, V.K., Isaacs, S.N., Separate worlds set to collide: Smallpox, vaccinia virus vaccination, and HIV/AIDS. Clinical Infectious Diseases 37:426-432 (2003).
Isaacs, S.N., Working safely with vaccinia virus. Methods in Molecular Biology - Vaccinia virus and Other Poxvirus Protocols [in press]
Kwak, H., Mustafa, W., Abdool, A.J., Paterson, Y., Isaacs, S.N. Improved protection conferred by vaccination with a recombinant vaccinia virus that incorporates a foreign antigen into the extracellular enveloped virion. [submitted for publication]
Kaslow , D.C. , Isaacs, S.N., Quakyi, I.A., Gwadz, R.W., Moss, B., Kiester, D.B., "Induction of Plasmodium falciparum Transmission Blocking Antibodies by Recombinant Vaccinia Virus" Science, 252:1310 (1991).
Isaacs, S.N., Wolffe, E.J., Payne, L.G., Moss, B., "Characterization of a Vaccinia Virus Encoded 42-kDa Class I Membrane Glycoprotein Component of the Extracellular Virus Envelope" Journal of Virology, 66:7217 (1992).
Herrera, E., Lorenzo, M., Blasco, R., Isaacs, S.N., "Functional Analysis of the Vaccinia Virus B5R-protein: Essential Role in Virus Envelopment is Independent of a Large Portion of the Extracellular Domain" Journal of Virology, 72:294-302 (1998).
Lorenzo, M., Herrera, E., Blasco, R., Isaacs, S.N., "Functional Analysis of Vaccinia Virus B5R Protein: Role of the Cytoplasmic Tail" Virology, 252:450-457 (1998)
Isaacs, S.N., Yi, Y., Singh A., Collman, R.G., "A macrophage fusion assay for rapid screening of cloned HIV-1 Env using dual recombinant vaccinia viruses expressing distinct RNA polymerases" Journal of Virological Methods [in press]
