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

Autor:	Marques-Neto LM; Laboratório de Desenvolvimento de Vacinas, Instituto Butantan, São Paulo, Brazil., Trentini MM; Laboratório de Desenvolvimento de Vacinas, Instituto Butantan, São Paulo, Brazil., Kanno AI; Laboratório de Desenvolvimento de Vacinas, Instituto Butantan, São Paulo, Brazil., Rodriguez D; Laboratório de Desenvolvimento de Vacinas, Instituto Butantan, São Paulo, Brazil., Leite LCC; Laboratório de Desenvolvimento de Vacinas, Instituto Butantan, São Paulo, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Jul 13; Vol. 14, pp. 1205449. Date of Electronic Publication: 2023 Jul 13 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1205449
Abstrakt:	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. Competing Interests: LL has a patent application on the use of rBCG-LTAK63 as a vaccine against Mtb. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Marques-Neto, Trentini, Kanno, Rodriguez and Leite.)
Databáze:	MEDLINE
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