Development of vaccines based on recombinant BCG: Tuberculosis, Pertussis, Pneumococcus and Schistosoma

Abstract

Our studies have demonstrated the advantages of Mycobacterium bovis BCG as an antigen presenting system in the development of new vaccines. The project aims to expand the use of methods of heterologous gene expression in BCG developed in our laboratories with the aim of proposing new vaccines in the immunization against Pertussis, Tuberculosis, Pneumococcus and Schistosome, and to improve the immunotherapeutic treatment of Bladder Cancer. Some proposals are more advanced, such as the recombinant BCG (rBCG) vaccine against Neonatal Pertussis and the rBCG strain used for improved treatment against Bladder Cancer that are heading for clinical trials. The rBCG strain expressing an E. coli antigen as adjuvant, which was shown to induce greater protection against Tuberculosis, completed the proof of concept phase and it should be further characterized. The establishment of the CRISPR/Cas9 platform and the Systems Biology approach will boost these studies. We have extensive research on pneumococcal antigens under different forms of presentation. The association of this information with the advantages of rBCG has been shown to be a promising approach. Schistosoma functional genomics provided a number of genes / proteins that have been characterized as potential vaccine candidates, but require a more immunogenic presentation to the immune system. We will investigate new expression vectors in rBCG and a new strategy, MAPS (Multiple Antigen Presenting System), aiming to improve the induction of immune responses and protection. Immune responses induced by rBCG strains will be compared to other forms of antigen presentation in search for correlates of protection. The results of each of the subprojects are expected to generate effective immunobiologicals against major diseases in the public health context of the country to enable large-scale, low-cost production. (AU)