Recombinant BCG expressing the LTAK63 adjuvant increased memory T cells and induced long-lasting protection against Mycobacterium tuberculosis challenge in mice

Author(s)

Marques-Neto, Lazaro Moreira ; Trentini, Monalisa Martins ; Kanno, Alex Issamu ; Rodriguez, Dunia ; Leite, Luciana Cezar de Cerqueira

• Document type: Journal article
• Source: FRONTIERS IN IMMUNOLOGY; v. 14, p. 11-pg., 2023-07-13.

Abstract

Vaccine-induced protection against Mycobacterium tuberculosis (Mtb) is usually ascribed to the induction of Th1, Th17, and CD8(+) T cells. However, protective immune responses should also involve other immune cell subsets, such as memory T cells. We have previously shown improved protection against Mtb challenge using the rBCG-LTAK63 vaccine (a recombinant BCG strain expressing the LTAK63 adjuvant, a genetically detoxified derivative of the A subunit from E. coli heat-labile toxin). Here we show that mice immunized with rBCG-LTAK63 exhibit a long-term (at least until 6 months) polyfunctional Th1/Th17 response in the draining lymph nodes and in the lungs. This response was accompanied by the increased presence of a diverse set of memory T cells, including central memory, effector memory and tissue-resident memory T cells. After the challenge, the T cell phenotype in the lymph nodes and lungs were characterized by a decrease in central memory T cells, and an increase in effector memory T cells and effector T cells. More importantly, when challenged 6 months after the immunization, this group demonstrated increased protection in comparison to BCG. In conclusion, this work provides experimental evidence in mice that the rBCG-LTAK63 vaccine induces a persistent increase in memory and effector T cell numbers until at least 6 months after immunization, which correlates with increased protection against Mtb. This improved immune response may contribute to enhance the long-term protection. (AU)

• FAPESP's process: 19/06454-0 - Evaluation of BCG expressing adjuvant LTAK63 in a humanized mouse model as a therapeutic vaccine for Tuberculosis
• Grantee: Monalisa Martins Trentini
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/02305-0 - Investigation of immune response mechanisms effective of a BCG Vaccine Recombinant against Tuberculosis by Systems Biology
• Grantee: Lázaro Moreira Marques Neto
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/24832-6 - Development of vaccines based on recombinant BCG: Tuberculosis, Pertussis, Pneumococcus and Schistosoma
• Grantee: Luciana Cezar de Cerqueira Leite
• Support Opportunities: Research Projects - Thematic Grants