Department of Microbiology

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Faculty Profile

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Fred Robert Frankel, Ph.D.

Emeritus Professor of Microbiology
Department: Microbiology

Contact information
Department of Microbiology
203 C Johnson Pavilion/6076
Philadelphia, PA 19104
Office: 2158988730
Graduate Group Affiliations
Education:
B.S. (Chemistry)
Pennsylvania State University, 1955.
M.S. (Biochemistry)
Pennsylvania State University, 1957.
Ph.D. (Biochemistry)
University of Florida, 1960.
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Description of Research Expertise

Keywords: Listeria monocytogenes, HIV infection, vaccine

Research Description:
Genetically altered forms of the bacterium Listeria monocytogenes for use as live vaccine vectors.

Research Summary:
Vaccines are often the most practical approach to the control of infectious diseases, and for viral infections may be the only means of control. Viral infections can be blocked by neutralizing antibodies, but chronic infections like HIV may require cell-mediated immune responses. Live vaccine vectors induce cell-mediated immunity most effectively. Consequently, we have been developing genetically altered forms of the bacterium Listeria monocytogenes for use as a live vaccine vector especially for the potential control of human immunodeficiency virus infections. In a mouse model, recombinants of Listeria monocytogenes induce a strong cell-mediated immune response directed against cells expressing HIV proteins. However, this organism cannot be used for human infections until its interaction with human or primate cells is more thoroughly examined, and until immunologically effective, but safely disabled strains of the organism become available. We have produced such a disabled strain and with collaborators have begun a small trial to test this vaccine in monkeys. The monkey experiments are going well. However, we have much work to do. For example, in mice we can induce protective immunity after oral immunization but don't know what component of the immune system is protecting. Also we want to enhance the antibody-inducing aspect of this vector and are trying various modifications to achieve this end. Finally, the strain is disabled by a requirement for supplementation with D-alanine, a rare amino acid not present in vertebrates. Immunogenicity is achieved by the transient supply of D-alanine along with the vaccine. We want to generate an organism that will supply its own D-alanine but under strictly controlled conditions so that its attenuation is not lost.

Selected Publications

Kushnir, N. and Frankel, F.R.: Attenuated Listeria monocytogenes: A live vaccine vector for infectious disease, cancer and AIDS. Recent Res. Devel. Infection & Immunity 2004.

Reayevskaya, 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.

Rayevskaya, M., Kushnir, N. and Frankel, F.R.: Safety and immunogenicity in neonatal mice of a hyperattenuated Listeria vacine directed against HIV. Journal of Virology(76), 918-922, 2002.

Rayevskaya MV., Frankel FR.: Systemic immunity and mucosal immunity are induced against human immunodeficiency virus Gag protein in mice by a new hyperattenuated strain of Listeria monocytogenes. Journal of Virology 75(6): 2786-91, Mar 2001.

Friedman RS., Frankel FR., Xu Z., Lieberman J.: Induction of human immunodeficiency virus (HIV)-specific CD8 T-cell responses by Listeria monocytogenes and a hyperattenuated Listeria strain engineered to express HIV antigens. Journal of Virology 74(21): 9987-93, Nov 2000.

Mata M., Travers PJ., Liu Q., Frankel FR., 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. Journal of Immunology 161(6): 2985-93, Sep 15 1998.

Thompson RJ., Bouwer HG., Portnoy DA., Frankel FR.: Pathogenicity and immunogenicity of a Listeria monocytogenes strain that requires D-alanine for growth. Infection & Immunity 66(8): 3552-61, Aug 1998.

Frankel FR., Hegde S., Lieberman J., Paterson Y.: Induction of cell-mediated immune responses to human immunodeficiency virus type 1 Gag protein by using Listeria monocytogenes as a live vaccine vector. Journal of Immunology 155(10): 4775-82, Nov 15 1995.

Ikonomidis G., Frankel FR., Portnoy DA., Paterson Y.: Listeria monocytogenes: a novel live vaccine vector. Vaccine 95 Cold Spring Harbor Laboratory Press, Page: 317-326, 1995.

Frankel FR., Steeger JR., Damiano VV., Sohn M., Oppenheim D., Weinbaum G.: Induction of unilateral pulmonary fibrosis in the rat by cadmium chloride. American Journal of Respiratory Cell & Molecular Biology 5(4): 385-94, Oct 1991.

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Last updated: 01/24/2013
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