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

Grant number: 17/24832-6
Support Opportunities:Research Projects - Thematic Grants
Duration: November 01, 2018 - October 31, 2023
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Luciana Cezar de Cerqueira Leite
Grantee:Luciana Cezar de Cerqueira Leite
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Pesquisadores principais:
Viviane Maimoni Gonçalves
Associated researchers:Alex Issamu Kanno ; Ana Carolina Ramos Moreno ; Celio Lopes Silva ; Dunia Del Carmen Rodriguez Soto ; Giovana Cappio Barazzone ; Helder Takashi Imoto Nakaya ; Ivan Pereira Nascimento ; Johnjoe McFadden ; Leonardo Paiva Farias ; Michelle Darrieux Sampaio Bertoncini ; Ricardo Carneiro Borra ; Richard Malley ; Robert Alan Wilson ; Sergio Costa Oliveira ; Sergio Verjovski Almeida
Associated scholarship(s):21/14376-9 - Optimization of SARS-CoV-2 antigen production in Expi293 cell culture aiming OMV-based vaccine generation, BP.MS
21/12711-5 - Recombinant BCG as a vaccine platform against COVID-19: construction of polyvalent vaccines for the most important SARS-CoV-2 variants, BP.PD
+ associated scholarships 21/12120-7 - Development of a vaccine against the SARS-CoV-2 Coronavirus using the new antigen presenting system (MAPS - OMV), BP.PD
20/14443-5 - Conjugation of antigens to the surface of BCG vaccine: application of the avidin-biotin system, BP.MS
20/05589-6 - 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, BP.DD
21/00145-5 - Development of a vaccine against the SARS-CoV-2 Coronavirus using the new antigen presenter system (MAPS - OMV), BP.TT
20/14758-6 - Development of a vaccine against the SARS-CoV-2 Coronavirus using the new Antigen Presenting System (MAPS - OMV), BP.PD
20/07547-9 - Development of a vaccine against Coronavirus SARS-CoV-2 using a new antigen presenting system, BP.PD
20/02049-0 - Strategies for monitoring and controlling the cultivation of recombinant BCG-pertussis, BP.MS
19/25728-3 - Evaluation of the role of POLIAMINAS PotD transporter in the formation of biofilm in vitro by Streptococcus pneumoniae, BP.IC
19/06454-0 - Evaluation of BCG expressing adjuvant LTAK63 in a humanized mouse model as a therapeutic vaccine for Tuberculosis, BP.PD
19/02305-0 - Investigation of immune response mechanisms effective of a BCG Vaccine Recombinant against Tuberculosis by Systems Biology, BP.PD - associated scholarships


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)

Articles published in Pesquisa para Inovação FAPESP about research grant:
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Scientific publications (22)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
OLIVEIRA, F. M.; MARINHO, F. V.; OLIVEIRA, S. C.; RESENDE, D. P.; JUNQUEIRA-KIPNIS, A. P.; KIPNIS, A.. Mycobacterium abscessus subsp. massiliense expressing bacterioferritin have improved resistance to stressful conditions. Journal of Applied Microbiology, v. 128, n. 6, . (17/24832-6)
ALEX I. KANNO; MAYRA M.F. BARBOSA; LUANA MORAES; LUCIANA C.C. LEITE. SARS-CoV-2 vaccine development and how Brazil is contributing. GENETICS AND MOLECULAR BIOLOGY, v. 44, n. 1, . (17/17218-0, 17/24832-6, 20/07547-9)
MAMBELLI, FABIO; SANTOS, BRUNO P. O.; MORAIS, SUELLEN B.; GIMENEZ, ENRICO G. T.; ASTONI, DUANA C. DOS S.; BRAGA, AMANDA D.; FERREIRA, RAFAELA S.; AMARAL, FLAVIO A.; DE MAGALHAES, MARIANA T. Q.; C. OLIVEIRA, SERGIO. S. mansoni SmKI-1 Kunitz-domain: Leucine point mutation at P1 site generates enhanced neutrophil elastase inhibitory activity. PLoS Neglected Tropical Diseases, v. 15, n. 1, . (17/24832-6)
DOS SANTOS, CARINA CARVALHO; RODRIGUEZ, DUNIA; ISSAMU, ALEX KANNO; DE CERQUEIRA LEITE, LUCIANA CEZAR; NASCIMENTO, IVAN PEREIRA. Recombinant BCG expressing the LTAK63 adjuvant induces increased early and long-term immune responses against Mycobacteria. HUMAN VACCINES & IMMUNOTHERAPEUTICS, v. 16, n. 3, p. 673-683, . (17/24832-6, 14/01271-0)
RODRIGUEZ, DUNIA; GOULART, CIBELLY; PAGLIARONE, ANA C.; SILVA, ELIANE P.; CUNEGUNDES, PRISCILA S.; NASCIMENTO, IVAN P.; BORRA, RICARDO C.; DIAS, WALDELY O.; TAGLIABUE, ALDO; BORASCHI, DIANA; et al. In vitro Evidence of Human Immune Responsiveness Shows the Improved Potential of a Recombinant BCG Strain for Bladder Cancer Treatment. FRONTIERS IN IMMUNOLOGY, v. 10, . (17/24832-6)
SANCHES, RODRIGO C. O.; SOUZA, CLAUDIA; MARINHO, FABIO VITARELLI; MAMBELLI, FABIO SILVA; MORAIS, SUELLEN B.; GUIMARAES, ERIKA S.; OLIVEIRA, SERGIO COSTA. NLRP6 Plays an Important Role in Early Hepatic Immunopathology Caused by Schistosoma mansoni Infection. FRONTIERS IN IMMUNOLOGY, v. 11, . (17/24832-6)
OLIVEIRA, SERGIO C.; DE MAGALHAES, MARIANA T. Q.; HOMAN, E. JANE. Immunoinformatic Analysis of SARS-CoV-2 Nucleocapsid Protein and Identification of COVID-19 Vaccine Targets. FRONTIERS IN IMMUNOLOGY, v. 11, . (17/24832-6)
FARIAS, LEONARDO P.; VANCE, GILLIAN M.; COULSON, PATRICIA S.; VITORIANO-SOUZA, JULIANA; NETO, ALMIRO PIRES DA SILVA; WANGWIWATSIN, ARPORN; NEVES, LEANDRO XAVIER; CASTRO-BORGES, WILLIAM; MCNICHOLAS, STUART; WILSON, KEITH S.; et al. Epitope Mapping of Exposed Tegument and Alimentary Tract Proteins Identifies Putative Antigenic Targets of the Attenuated Schistosome Vaccine. FRONTIERS IN IMMUNOLOGY, v. 11, . (12/23124-4, 17/24832-6)
KANNO, I, ALEX; BARBOSA, MAYRA M. F.; MORAES, LUANA; LEITE, LUCIANA C. C.. SARS-CoV-2 vaccine development and how Brazil is contributing. GENETICS AND MOLECULAR BIOLOGY, v. 44, n. 1, 1, . (17/17218-0, 17/24832-6, 20/07547-9)
PAGLIARONE, ANA CAROLINA; CASTANEDA, EDWIN DAVID; PEDOTT SANTANA, JHONNE PEDRO; DE OLIVEIRA, CAIO ALMEIDA; ROBELDO, THAIANE ALCARDE; TEIXEIRA, FELIPE ROBERTI; BORRA, RICARDO CARNEIRO. Mitochondrial heat shock protein mortalin as potential target for therapies based on oxidative stress. Photodiagnosis and Photodynamic Therapy, v. 34, . (17/24832-6)
CONVERSO, T. R.; ASSONI, L.; ANDRE, G. O.; DARRIEUX, M.; LEITE, L. C. C.. The long search for a serotype independent pneumococcal vaccine. EXPERT REVIEW OF VACCINES, v. 19, n. 1, . (17/24832-6)
MARINHO, FABIO V.; FAHEL, JULIA S.; DE ARAUJO, ANA CAROLINA V. S. C.; DINIZ, LUNNA T. S.; GOMES, MARCO T. R.; RESENDE, DANILO P.; JUNQUEIRA-KIPNIS, ANA P.; OLIVEIRA, SERGIO C.. Guanylate binding proteins contained in the murine chromosome 3 are important to control mycobacterial infection. Journal of Leukocyte Biology, . (17/24832-6)
SANCHES, RODRIGO C. O.. The role of the adaptor molecule STING during Schistosoma mansoni infection. SCIENTIFIC REPORTS, v. 10, n. 1, . (17/24832-6)
LARISSA V NASCIMENTO; CARINA C SANTOS; LUCIANA CC LEITE; IVAN P NASCIMENTO. Characterisation of alternative expression vectors for recombinant Bacillus Calmette-Guérin as live bacterial delivery systems. Memórias do Instituto Oswaldo Cruz, v. 115, . (17/24832-6, 14/01271-0)
MARQUES-NETO, LAZARO M.; PIWOWARSKA, ZUZANNA; KANNO, I, ALEX; MORAES, LUANA; TRENTINI, MONALISA M.; RODRIGUEZ, DUNIA; SILVA, JOSE L. S. C.; LEITE, LUCIANA C. C.. Thirty years of recombinant BCG: new trends for a centenary vaccine. EXPERT REVIEW OF VACCINES, v. 20, n. 8, . (17/24832-6)
DE QUEIROZ, NINA MARI G. P.; MARINHO, FABIO V.; CHAGAS, MARCELO A.; LEITE, LUCIANA C. C.; HOMAN, E. JANE; DE MAGALHAES, MARIANA T. Q.; OLIVEIRA, SERGIO C.. Vaccines for COVID-19: perspectives from nucleic acid vaccines to BCG as delivery vector system. Microbes and Infection, v. 22, n. 10, p. 515-524, . (17/24832-6)
SANCHES, RODRIGO C. O.; SOUZA, CLAUDIA; OLIVEIRA, SERGIO C.. Schistosoma antigens as activators of inflammasome pathway: from an unexpected stimulus to an intriguing role. Microbes and Infection, v. 22, n. 10, p. 534-539, . (17/24832-6)
SANTOS, B. P. O.; ALVES, E. S. F.; FERREIRA, C. S.; FERREIRA-SILVA, A.; GOES-NETO, A.; VERLY, R. M.; LIAO, L. M.; OLIVEIRA, S. C.; DE MAGALHAES, M. T. Q.. Schistocins: Novel antimicrobial peptides encrypted in the Schistosoma mansoni Kunitz Inhibitor SmKI-1. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, v. 1865, n. 11, . (17/24832-6)
ELIZAGARAY, MAIA L.; GOMES, MARCO TULIO R.; GUIMARAES, ERIKA S.; RUMBO, MARTIN; HOZBOR, DANIELA F.; OLIVEIRA, SERGIO C.; MORENO, GRISELDA. Canonical and Non-canonical Inflammasome Activation by Outer Membrane Vesicles Derived FromBordetella pertussis. FRONTIERS IN IMMUNOLOGY, v. 11, . (17/24832-6)
MAMBELLI, F. S.; FIGUEIREDO, B. C.; MORAIS, S. B.; ASSIS, N. R. G.; FONSECA, C. T.; OLIVEIRA, S. C.. Recombinant micro-exon gene 3 (MEG-3) antigens from Schistosoma mansoni failed to induce protection against infection but show potential for serological diagnosis. Acta Tropica, v. 204, . (17/24832-6)
DE QUEIROZ, NINA M. G. P.; MARINHO, FABIO V.; DE ARAUJO, ANA CAROLINA V. S. C.; FAHEL, JULIA S.; OLIVEIRA, SERGIO C.. MyD88-dependent BCG immunotherapy reduces tumor and regulates tumor microenvironment in bladder cancer murine model. SCIENTIFIC REPORTS, v. 11, n. 1, . (17/24832-6)

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