Bernhard Dietzschold, DVM
Professor, Microbiology and Immunology

Contact Dr. Dietzschold

233 S. 10th Street
Room 533
Philadelphia, PA 19107

(215) 503-4692

Education
Education

University Appointment
Professor
Microbiology and Immunology
Thomas Jefferson University

Research and Clinical Interests
Our laboratory focuses on the development of oral rabies vaccines for wildlife. Oral immunization with live vaccines is the only practical approach to eradicate rabies in free ranging animals. One approach for oral vaccination against rabies is the use of live attenuated rabies virus (RV) variants. Live rabies virus (RV) vaccines must be able to induce sufficient protective immunity after oral administration in all target species. Furthermore, live RV vaccines suitable for oral immunization must be safe and the nonpathogenic phenotype of the vaccine virus must be stable. To fulfill these criteria, we constructed recombinant viruses that express either one (SPBNGA) or two (SPBNGA-GA) glycoproteins (G). These Gs contain a Glu at position 333 that renders these viruses non-pathogenic. To further stabilize the non-pathogenic phenotype the Asn194 of G was exchanged with Ser194 resulting in SPBNGAS and SPBNGAS-GAS. In contrast to the GAN variants, the non-pathogenic phenotype of the GAS variants remained stable even after multiple passages in newborn mice, making these RV variants suitable as live vaccines for wild-life. Oral immunization of target animal species such as dogs, raccoons, and skunks with the GAS variants conferred protective immunity against a lethal challenge infection with RV. However, the efficacy of SPBNGAS-GAS was significantly higher than that of SPBNGAS, indicating that SPBNGAS-GAS will probably be the vaccine of choice to be used in wildlife vaccination campaigns.

Another approach in our laboratory to develop an effective oral rabies vaccine uses canine adenovirus 2 (CAV2) as a vaccine delivery vehicle. Because canine adenovirus 2 (CAV2) is licensed for use as a live vaccine for dogs and has an excellent efficacy and safety record, we used this virus as an expression vector for the RV G. The recombinant CAV2-RVG produces virus titers similar to those produced by wild-type CAV2, indicating that the RV G gene does not affect virus replication. A single intramuscular or intranasal immunization of mice with CAV2-RVG induced protective immunity in a dose-dependent manner, with no clinical signs or discomfort from the virus infection regardless of the route of administration or the amount of virus. The CAV2-RVG vaccine is currently being tested for efficacy and safety in a phase II trial.

Publications

1. Intramuscular inoculation of mice with the live-attenuated recombinant rabies virus TriGAS results in a transient infection of the draining lymph nodes and a robust, long-lasting protective immune response against rabies
2. Postexposure treatment with the live-attenuated rabies virus (rv) Vaccine trigas triggers the clearance of wild-type rv from the central nervous system (cns) Through the rapid induction of genes relevant to adaptive immunity in cns tissues
3. The Role of Toll-Like Receptors in the Induction of Immune Responses During Rabies Virus Infection
4. Oral immunization of raccoons and skunks with a canine adenovirus recombinant rabies vaccine
5. Development of a mouse monoclonal antibody cocktail for post-exposure rabies prophylaxis in humans
6. Immunogenicity and safety of recombinant rabies viruses used for oral vaccination of stray dogs and wildlife
7. Effective preexposure and postexposure prophylaxis of rabies with a highly attenuated recombinant rabies virus
8. Intravenous inoculation of a bat-associated rabies virus causes lethal encephalopathy in mice through invasion of the brain via neurosecretory hypothalamic fibers
9. Immune modulating effect by a phosphoprotein-deleted rabies virus vaccine vector expressing two copies of the rabies virus glycoprotein gene
10. Concepts in the pathogenesis of rabies
11. Role of virus-induced neuropeptides in the brain in the pathogenesis of rabies
12. The glycoprotein and the matrix protein of rabies virus affect pathogenicity by regulating viral replication and facilitating cell-to-cell spread
13. Infection of monocytes or immature dendritic cells (DCs) with an attenuated rabies virus results in DC maturation and a strong activation of the NFκB signaling pathway
14. Oral vaccination of raccoons (Procyon lotor) with genetically modified rabies virus vaccines
15. Dominance of a nonpathogenic glycoprotein gene over a pathogenic glycoprotein gene in rabies virus
16. Highly attenuated rabies virus-based vaccine vectors expressing simian-human immunodeficiency virus89.6P Env and simian immunodeficiency virusmac239 Gag are safe in rhesus macaques and protect from an AIDS-like disease
17. A single immunization with a recombinant canine adenovirus expressing the rabies virus G protein confers protective immunity against rabies in mice
18. Rabies virus glycoprotein as a carrier for anthrax protective antigen
19. Vaccination of small Asian mongoose (Herpestes javanicus) against rabies
20. Comparison of an anti-rabies human monoclonal antibody combination with human polyclonal anti-rabies immune globulin

(This list reflects the most recent 20 publications)