Fred R. Frankel, Ph.D.

Professor of Microbiology

Office Address:
Department of Microbiology
Perelman School of Medicine
University of Pennsylvania
203 C Johnson Pavilion
3610 Hamilton Walk
Philadelphia, PA 19104-6076

TEL 215-898-8730
LAB 215-573-8543
FAX 215-898-9557
frankelf@mail.med.upenn.edu

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.