Investigation of the mechanisms of innate immune response activation induced by rBCG-LTAK63 and rBCG-S1PT vaccines: autophagy and inflammasome activation

• Grant number: 22/13917-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2023
• End date: September 30, 2024
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Alex Issamu Kanno
• Grantee: Ana Carolina de Oliveira Carvalho
• Host 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

BCG is one of the most widely used vaccines in the world. BCG has many attractive characteristics that make it an interesting vector in the presentation of heterologous antigens and, consequently, in the development of new vaccines. In addition, several studies have shown that immunization with BCG induces nonspecific protection against other infectious diseases. This protection indicates the involvement of innate immunity, a phenomenon termed "innate immune memory" or "trained immunity". In the field of vaccinology, innate events are in current evidence given their influence on the acquired immune response. Autophagy and inflammasome activation are mechanisms related to the innate immune response and their action leads to improved antigen presentation and processing by antigen-presenting cells. Our laboratory has developed a vaccine based on recombinant BCG expressing LTAK63 (rBCG-LTAK63), a genetically detoxified version of the thermolabile LT toxin from E. coli. Immunization with rBCG-LTAK63 was able to induce protection in mice challenged with Mycobacterium tuberculosis (Mtb), and also promoted increased production of reactive oxygen and nitrogen species. Another vaccine produced in the lab, rBCG-S1PT, expresses the genetically detoxified S1 subunit of Bordetella pertussis. This vaccine induced protection in mice immunized against B. pertussis challenge, in addition to a superior innate immune response to the parental BCG. Based on this, this project aims to investigate the innate immune processes of autophagy and inflammasome activation induced by rBCG-LTAK63 and rBCG-S1PT vaccines.