Recombinant BCG expressing Schistosoma mansoni surface antigens: immune response and protection assessment

Abstract

Schistosomiasis is a parasitic disease that affects between 200-300 million individuals around the world and is endemic in more than 70 countries, characterizing it as a public health problem. Despite the effectiveness of chemotherapy, it does not protect against reinfection and the development of a vaccine would be very beneficial. The use of live vectors for the presentation of heterologous antigens is an attractive idea, because it would eliminate the necessity for multiple doses to achieve maximum protection. This work aims to investigate the potential of BCG vaccines based on expression of antigens of Schistosoma mansoni identified in the studies of functional genomics. Possible antigens of the parasite to be tested would be: Sm29 - a tegument membrane protein, a Venom-Allergen-Like Protein (VAL), a stomatin and a tetraspanin. The genes of these antigens will be cloned into mycobacterial expression vectors under the control of the upregulated Mycobacterium fortuitum beta-lactamase promoter, pBlaF*, in fusion or not with either the beta-lactamase signal sequence or the whole beta-lactamase protein. These vectors have a kanamycin selection marker. The alfa-antigen of M. kansasii could be used in fusion with the antigens as an exportation strategy and/or to increase their level of expression. Mice will be immunized with the recombinant BCG strains constructed and the induced humoral e cellular immune response assessed. The animals will then be submitted to challenge with S. mansoni cercarie to determine the protection conferred by immunization with the different strains of rBCG. (AU)