Study of the mechanisms responsible for trained immunity induced by Bacillus Calmette-Guérin (BCG) in infectious diseases and Cancer

• Grant number: 23/02577-5
• Support Opportunities: Research Projects - Thematic Grants
• Start date: May 01, 2024
• End date: April 30, 2029
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Sergio Costa Oliveira
• Grantee: Sergio Costa Oliveira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Alex Issamu Kanno ; Ana Carolina Ramos Moreno ; Dunia Del Carmen Rodriguez Soto ; João Gustavo Pessini Amarante Mendes ; João Santana da Silva ; Luciana Cezar de Cerqueira Leite ; Luis Carlos de Souza Ferreira
• Associated research grant(s): 24/19233-0 - The role of STING in trained innate immunity to improve cancer immunotherapy., AP.R SPRINT; 24/12744-9 - Multi-user equipment approved in grant 2023/02577-5: Amersham Imagequant 800, AP.EMU
• Associated scholarship(s): 25/20947-0 - Study of BCG immunotherapy mediated by the adaptor molecule MyD88 in tumor control., BP.TT; 25/03267-5 - The combined use of anti-PD1 antibodies and intravesical immunotherapy with rBCG-LTAK63 to enhance bladder cancer treatment in a murine orthotopic model., BP.MS; 25/11180-7 - STING-mediated mechanisms in BCG-trained immunity during Brucella abortus infection., BP.PD; + associated scholarships 24/07426-8 - Evaluation of innate immune memory in the antitumor efficacy of an immunotherapy based on recombinant BCG, BP.IC; 24/09989-0 - Evaluation of the antitumor effect of the therapeutic association between recombinant BCG and interleukin-15 super agonist in a murine model of orthotopic bladder cancer, BP.IC; 24/12935-9 - Phenotypic and functional analysis of innate immune response cells from bladder cancer patients as a proof of concept for the immunostimulatory effect of recombinant BCG, BP.DR; 24/13812-8 - Evaluation of the role of BCG-induced trained immunity in activating the innate immune response during Brucella abortus infection, BP.DD; 24/09721-7 - Technical Support for cell culture and molecular biology, BP.TT - associated scholarships

Abstract

The Bacillus Calmette-Guérin (BCG) besides its specific action against tuberculosis, it has the ability to trigger non-specific positive effects against heterologous viral and bacterial infections and against cancer. These effects have been associated in part with the innate immune system through a phenomenon termed trained immunity that is long lasting when it involves bone marrow cells (BM). The molecular basis of trained immunity in the monocyte/macrophage lineage has been the focus of intense investigation in the last decade; however, several scientific gaps still exist to explain this unspecific protective effect induced by BCG. In this context, there is a great importance of the metabolic and epigenetic reprogramming in host cells induced by BCG that will be investigated in this proposal. Our working hypothesis is based on the ability of trained immunity induced by BCG to protect against infections caused by the SARS-CoV-2 virus and the bacteria Brucella abortus, and against cancer. To test this hypothesis the main goal of this project is to investigate the mechanisms of protection mediated by trained immunity induced by BCG against SARS-CoV-2 and Brucella abortus infections and against murine models of cancer. This is a multidisciplinary project divided in three proposals that involve scientists from different institutions in the state of São Paulo such as: University of São Paulo (Departments of Immunology and Microbiology), Fiocruz- Bi-Institutional Translational Medicine Project (Ribeirão Preto-SP) and the Butantan Institute (Laboratory of Vaccine Development). (AU)

Scientific publications

(6)

(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)

OLAGUNJU, ABOLAJI S.; SARDINHA, ANDREW V. D.; AMARANTE-MENDES, GUSTAVO P.. Long-Lasting, Fine-Tuned Anti-Tumor Activity of Recombinant Listeria monocytogenes Vaccine Is Controlled by Pyroptosis and Necroptosis Regulatory and Effector Molecules. PATHOGENS, v. 13, n. 10, p. 11-pg., 2024-10-01. (21/07624-6, 21/13486-5, 21/12143-7, 23/02577-5, 18/25395-1)

MARINHO, FABIO V.; BRITO, CAMILA; DE ARAUJO, ANA CAROLINA V. S. C.; OLIVEIRA, SERGIO C.. Guanylate-binding protein-5 is involved in inflammasome activation by bacterial DNA but only the cooperation of multiple GBPs accounts for control of Brucella abortus infection. FRONTIERS IN IMMUNOLOGY, v. 15, p. 12-pg., 2024-02-08. (22/15358-7, 23/02577-5, 23/09226-3)

GUIMARAES, ERIKA S.; GOMES, MARCO TULIO R.; MORAES-VIEIRA, PEDRO M.; OLIVEIRA, SERGIO C.. Brucella abortus induces dynamin-related protein 1 (DRP1)-dependent mitochondrial fission in infected macrophages via stress sensor IRE1α altering metabolic function. JOURNAL OF IMMUNOLOGY, v. N/A, p. 13-pg., 2025-08-14. (24/12744-9, 23/02577-5, 22/15358-7, 23/09226-3)

MAMBELLI, FABIO; DE ARAUJO, ANA CAROLINA V. S. C.; FARIAS, JESSICA P.; DE ANDRADE, KIVIA Q.; FERREIRA, LUIS C. S.; MINOPRIO, PAOLA; LEITE, LUCIANA C. C.; OLIVEIRA, SERGIO C.. An Update on Anti-COVID-19 Vaccines and the Challenges to Protect Against New SARS-CoV-2 Variants. PATHOGENS, v. 14, n. 1, p. 19-pg., 2025-01-01. (23/01925-0, 23/03874-3, 23/09226-3, 17/27131-9, 23/02577-5, 23/11077-6)

GOMES, MARCO TULIO R.; GUIMARAES, ERIKA S.; OLIVEIRA, SERGIO C.. ZBP1 senses Brucella abortus DNA triggering type I interferon signaling pathway and unfolded protein response activation. FRONTIERS IN IMMUNOLOGY, v. 15, p. 11-pg., 2025-01-09. (22/15358-7, 23/02577-5)

BORGES, VINICIUS M.; MARINHO, FABIO V.; CALDEIRA, CHRISTIANE V. A.; DE QUEIROZ, NINA M. G. P.; OLIVEIRA, SERGIO C.. Bacillus Calmette-Guérin immunotherapy induces an efficient antitumor response to control murine melanoma depending on MyD88 signaling. FRONTIERS IN IMMUNOLOGY, v. 15, p. 15-pg., 2024-05-21. (23/02577-5, 17/24832-6, 23/06778-5)