Immunological characterization of a recombinant BCG strain that simultaneously expresses mutant Pertussis toxin S1PT and adjuvant LTAK63 (rBCG-LTAK63-S1PT) for use as a bivalent vaccine to prevent Neonatal Pertussis and Tuberculosis

• Grant number: 20/05589-6
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: March 01, 2021
• End date: September 30, 2021
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Celio Lopes Silva
• Grantee: Aline Seiko Carvalho Tahyra
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , 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) persists among the main causes of death from infectious diseases, killing more than 1.5 million people annually, mainly in developing countries (WHO, 2019). BCG - the only approved vaccine for TB prevention - is relatively effective in children, but protection is reduced and limited in adults. Our group has been working for more than 20 years in the research and development of preventive and therapeutic vaccines for TB. The development of new TB vaccines is one of WHO's priorities and recombinant BCG (rBCG) strategies are attractive and recommended. In a recent study developed by the Butantan Institute, in partnership with our group, we demonstrated that a new strain of rBCG that expresses the genetically detoxified E. coli adjuvant protein LTAK63 (rBCG-LTAK63) has greater protection against TB than the original BCG (Nascimento et al., 2017). On the other hand, there has recently been an increase in Pertussis cases, mainly affecting neonates, and Butantan has developed a vaccine prototype, based on rBCG, which expresses the genetically detoxified Pertussis toxin S1PT (rBCG-S1PT). This vaccine construction demonstrated protection in newborn mice against the challenge by Bordetella Pertussis (Nascimento et al., 2008). Thus, the objective of this project is to use platforms established by the proponent groups of the thematic project (CRISPR/Cas9, Systems Biology approach and optimization of rBCG constructions) to build a rBCG strain that expresses both LTAK63 and S1PT (rBCG-LTAK63-S1PT ), which will be tested as a bivalent vaccine for greater protection for both TB and pertussis. The rBCG-LTAK63-S1PT vaccine, under construction, will be evaluated for stability of expression of cloned genes, induction of innate and adaptive immune response, and vaccine efficacy, compared to the constructions of the respective original vaccines. It is expected at the end of the project to have a bivalent vaccine rBCG-LTAK63-S1PT capable of protecting mice against TB and neonatal Pertussis. (AU)