STUDIES ON PROTECTIVE EFFECTS OF A VACCINE, BASED ON RECOMBINANT Ag85, TB10 AND FliC PROTEINS

At present time, there is an obvious need for a new generation of vaccines as the most effective preventive approach, in order to stop spreading of tuberculosis infection. So far, the most popular strategy is aimed at heterological vaccination. The idea is to use BCG, or improved BCG, or attenuated M. tuberculosis for primary vaccination. For the further booster vaccination one may apply thw s.c. subunit or vector vaccines, containing protective mycobacterial proteins. The aim of our investigation was to evaluate protective effects of a new vaccine based on recombinant bacterial proteins Ag85, ТВ10 and FliC. We used a model with aerosol M. tuberculosis H37Rv infection, and compared lung and spleen CFU counts and life-span of vaccinated versus non-vaccinated С57BL/6 mice. As a result, we revealed three vaccine variants with comparable protective capacity against BCG using our experimental model. The most promising variant is suggested for testing in preclinical trials

DURATION OF IMMUNE RESPONSE INDUCED BY THE VACCINE BASED ON RECOMBINANT Ag85, TB10 AND FliC PROTEINS

Already about one hundred years BCG remains the only widely used tuberculosis (TB) vaccine. It is known that intensity of the BCG-induced Th1 immune response decreases over time and comes to naught within 10-15 years. It significantly distinguishes BCG from the vaccines providing a lifelong protection such as vaccines against poliomyelitis or measles, and can be bound to natural restriction of duration of a persistence of the BCG-induced CD4+ T-cells. Data on insufficient ability of BCG to stimulate life-long immunological memory is accumulating. Earlier in our lab on the model of rather resistant to TB C57BL/6 mice infection with the virulent laboratory strain of Mycobacterium tuberculosis (Mtb) H37Rv protective activity (comparable to that of BCG Russia) of 3 subunit vaccine variants was demonstrated as assessed by lung and spleen CFU counts and life span of animals after infection. The aim of this study was to study the characteristics and duration of the immune response induced by the most effective variant of these vaccines. Groups of C57BL/6 mice were vaccinated intramuscularly twice with two-week intervals with 10 μg protein conjugated to 200 μl of an aluminum hydroxide emulsion. Immune response (production of specific antibodies, vaccine proteinstimulated production of interferon gamma and proliferation in vitro) was monitored during 10 months after vaccination. We have shown that the test vaccine induces in mice the formation of long-term immunological memory to a bacterial antigen. Moreover, in the presence of glutoxim the immunological memory spectrum shifts to a "protective" type, i.e. the predominance of the cellular component of the immune response over the antibody response is stimulated. The next step will be the investigation of vaccine effectiveness for revaccination after primary BCG immunization