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Member Information
Fred R. Frankel, PhD
Professor, Department of Microbiology
Office Phone: 215-898-8730
Office Fax:
Email: frankelf@mail.med.upenn.edu
Website(s):
Education: PhD 1960, University of Florida
Keywords: Listeria monocytogenes, HIV infection, vaccine
Research and/or Clinical Interests:
Genetically altered forms of the bacterium Listeria monocytogenes for use as live vaccine vectors.
Summary:
Vaccines are often the most practical approach to the control of infectious diseases, and, in the case of many viral infections, they may constitute the only means for control. Often viral infections are terminated by cell-mediated immune responses, and these responses are induced most effectively by live vaccine vectors. Consequently, we have been developing genetically altered forms of the bacterium Listeria monocytogenes for use as live vaccine vectors especially for the potential control of human immunodeficiency virus infections. In our mouse model, recombinants of Listeria monocytogenes appear to induce a strong cell-mediated immune response directed against cells expressing HIV proteins. We are now beginning a trial to test this vaccine in monkeys. However, such a vaccine cannot be used for human infections until the interaction of this bacterium with human cells is more thoroughly examined, and until immunologically effective, but safely disabled strains of the organism become available. We have made significant progress in studies of these two important issues.
Representative Publications:
Friedman, R.S., Frankel, F.R., Xu, Z. and Lieberman, J. Induction of HIV-specific CD8 T cell responses by Listeria monocytogenes and a hyper-attenuated Listeria strain engineered to express HIV antigens. J. Virol. 74:9987-9993, 2000.
Rayevskaya, M. and Frankel, F.R. Systemic and mucosal immunity are induced against HIV-gag protein in mice by a new hyperattenuated strain of Listeria monocytogenes . J. Virol, 75:2786-2791, 2001.
Rayevskaya, M., Kushnir, N. and Frankel, F.R. Safety and immunogenicity in neonatal mice of a hyperattenuated Listeria vaccine directed against HIV, J. Virol, 76:918-922, 2002.
Kushnir, N. and Frankel, F.R. Attenuated Listeria monocytogenes : A live vaccine vector for infectious disease, cancer and AIDS. Recent Res. Devel. Infection & Immunity, In press, 2003.
Rayevskaya, M., Kushnir, N., and Frankel, F.R. Anti-HIV-gag CD8 + memory T cells generated in vitro from Listeria -immunized mice. Immunology, 109:450-460, 2003.
Thompson, R.J., Bouwer, A., Portnoy, D.A., and Frankel, F.R. D. Pathogenicity and immunogenicity of a D-alanine-requiring strain of Listeria monocytogenes. Infection and Immunity, 66: 3552-3561, 1998.
Mata, M., Travers, P., Frankel, F. R., and Paterson, Y. The MHC class I restricted immune response to HIV-gag in BALB/c mice selects a single epitope that does not have a predictable MHC binding motif and binds to Kd through interactions between a glutamine at P3 and pocket D. J.Immunol. 161: 2985-2993, 1998.
