Strategies for monitoring and controlling the cultivation of recombinant BCG-pertussis

• Grant number: 20/02049-0
• Support type: Scholarships in Brazil - Master
• Effective date (Start): June 01, 2020
• Effective date (End): February 28, 2022
• Field of knowledge: Engineering - Chemical Engineering
• Principal Investigator: Viviane Maimoni Gonçalves
• Grantee: Lucas de Souza Borban
• Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 17/24832-6 - Development of vaccines based on recombinant BCG: Tuberculosis, Pertussis, Pneumococcus and Schistosoma, AP.TEM

Abstract

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis and is one of the main causes of death in the world. The attenuated live vaccine produced with the Calmette-Guérin bacillus (BCG) is the only one available against human TB and it is administrated as one dose on birth. However, BCG has low efficiency against pulmonary TB in adolescents and adults, and for this reason, vaccines are extremely necessary to fight this disease. The whooping cough is a highly contagious acute respiratory infection caused by the bacterium Bordetella pertussis. Nowadays, the pertussis vaccines are administrated in 3 doses on 2-6 months old, with the most vulnerable age group (<6 months) left partially or entirely unprotected. So, our group developed a rBCG-pertussis strain, which not only induces more efficient protective immunity against TB, but also provides protection against B. pertussis on newborn mice. Besides, rBCG-pertussis was more efficient for the treatment of bladder cancer in an animal model than the conventional onco-BCG. Despite advances in the understanding of mycobacteria and several proposals for the application of rBCG, there is little data on the cultivation of this microorganism in bioreactors and BCG is still produced in a fairly handmade way in static flasks. Therefore, this project has the purpose of establishing strategies for monitoring and controlling biomass formation and cellular viability of rBCG-pertussis in submerged cultures carried out in bioreactors. Hence, it is expected to contribute to the development of a modern process for the cultivation of rBCG-pertussis in bioreactors, which presents greater reproducibility and reduces failures and contamination compared to static cultivation, moreover, a process that reaches high cellular density and viability. (AU)