Vaccines R&D & Vaccination

Adel M Talaat is a Microbiologist with a long-term interest in better understanding the pathogenesis of emerging infectious diseases. He has received his Veterinary and Masters’ degrees from Cairo University, Egypt and a PhD from the School of Medicine University of Maryland At Baltimore, USA. Currently, he is a Professor of Microbiology at the University of Wisconsin-Madison. His research involves developing new technologies and innovative approaches to understand bacterial pathogenesis and to generate useful therapies (drugs and vaccines). Currently, we are working on the functional genomics of Mycobacterium tuberculosis and M. avium subsp. paratuberculosis. Recently, he and his group started to utilize nanotechnology to develop nano-biosensors and nanovaccines to control animal infections, including avian viral agents. In 2011, he started a biotechnology company (Pan Genome Systems, INC.) to further develop intellectual properties generated by his group (vaccine-based patents) into products useful to improve human and animal health. During the past decade, he has mentored 17 Undergraduates, 19 Graduate students and 10 Postdoctoral fellows in his laboratory at the University of Wisconsin-Madison. The results of his career at UW-Madison were shared through more than 50 articles in peer-reviewed journals.

The current tuberculosis vaccine, M. bovis BCG (BCG), has variable protection levels ranging from 0-80%, depending on the country of application and the genotype of vaccine used. The reductionists approach (depending on a selected list of antigens) for developing tuberculosis vaccines, did not identify any better alternatives to BCG, especially when candidates are tested under clinical setting in countries with high tuberculosis prevalence (e.g. South Africa). Earlier research from our group has identified several M. tuberculosis mutants that were further developed into live attenuated vaccine (LAV) candidates against TB. Our working hypothesis is that potent LAV will induce a broader and more potent memory T-cell response, will be more effective against highly virulent M. tuberculosis clinical isolates, and will be able to counteract the activity of regulatory T cells, three areas in which BCG performs very poorly. Using a stringent aerosol model of murine challenge, immunization with two candidates (M. tb mosR, M. tb echA7) significantly reduced the M. tb load in murine tissues. Remarkably, by 60 days post challenge (DPC), no colonization was observed in organs of the mosR-vaccinated mice. Immunologically, flow cytometry of lymphocytes isolated from the lung revealed that echA7 primed a significantly greater CD4+ IFN-γ response than either mosR or BCG. ELISA assays at 60 DPC demonstrated significantly higher M. tuberculosis specific IFN-γ production by splenocytes isolated from mice vaccinated with echA7 compared to the others. Interestingly, by eight weeks post immunization (WPI), mosR was found only in the spleen of one immunized mice. Another experiment with high and low doses of mosR-LAV did not alter any of the mice health parameters, another testimony of the safety of mosR-LAV. Currently, we are testing a novel construct of a double gene knockout MTBLAV (mosR echA7) using a novel vector system developed by our group. In this communication, we are going to discuss findings from our group on the performance of MTBLAV in relation to other leading vaccine candidates designed to combat tuberculosis. Our main goal is to end the suffering from tuberculosis using targeted vaccines towards specific populations.