Recombinant BCG expressing the LTAK63 adjuvant improves a short-term chemotherapy schedule in the control of tuberculosis in mice
Tuberculosis (TB) is one of the deadliest infectious diseases around the world. Prevention is based on the prophylactic use of BCG vaccine, effective in infants but as protection wanes with time, adults are less protected. Additionally, chemotherapy requires the use of many antibiotics for several m...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.943558/full |
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| author | Monalisa Martins Trentini Alex Issamu Kanno Dunia Rodriguez Lazaro Moreira Marques-Neto Silas Fernandes Eto Silas Fernandes Eto Ana Marisa Chudzinki-Tavassi Ana Marisa Chudzinki-Tavassi Luciana Cezar de Cerqueira Leite |
| author_facet | Monalisa Martins Trentini Alex Issamu Kanno Dunia Rodriguez Lazaro Moreira Marques-Neto Silas Fernandes Eto Silas Fernandes Eto Ana Marisa Chudzinki-Tavassi Ana Marisa Chudzinki-Tavassi Luciana Cezar de Cerqueira Leite |
| author_sort | Monalisa Martins Trentini |
| collection | DOAJ |
| description | Tuberculosis (TB) is one of the deadliest infectious diseases around the world. Prevention is based on the prophylactic use of BCG vaccine, effective in infants but as protection wanes with time, adults are less protected. Additionally, chemotherapy requires the use of many antibiotics for several months to be effective. Immunotherapeutic approaches can activate the immune system, intending to assist chemotherapy of TB patients, improving its effectiveness, and reducing treatment time. In this work, the recombinant BCG expressing LTAK63 (rBCG-LTAK63) was evaluated for its immunotherapeutic potential against TB. Bacillary load, immune response, and lung inflammation were evaluated in mice infected with Mycobacterium tuberculosis (Mtb) and treated either with BCG or rBCG-LTAK63 using different routes of administration. Mice infected with Mtb and treated intranasally or intravenously with rBCG-LTAK63 showed a reduced bacillary load and lung inflammatory area when compared to the group treated with BCG. In the spleen, rBCG-LTAK63 administered intravenously induced a higher inflammatory response of CD4+ T cells. On the other hand, in the lungs there was an increased presence of CD4+IL-10+ and regulatory T cells. When combined with a short-term chemotherapy regimen, rBCG-LTAK63 administered subcutaneously or intravenously decreases the Mtb bacillary load, increases the anti-inflammatory response, and reduces tissue inflammation. These findings highlight the potential of rBCG-LTAK63 in assisting chemotherapy against Mtb. |
| first_indexed | 2024-04-13T23:39:02Z |
| format | Article |
| id | doaj.art-773bbf48f4ca4016bd1f8efd6dccce1d |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T23:39:02Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-773bbf48f4ca4016bd1f8efd6dccce1d2022-12-22T02:24:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.943558943558Recombinant BCG expressing the LTAK63 adjuvant improves a short-term chemotherapy schedule in the control of tuberculosis in miceMonalisa Martins Trentini0Alex Issamu Kanno1Dunia Rodriguez2Lazaro Moreira Marques-Neto3Silas Fernandes Eto4Silas Fernandes Eto5Ana Marisa Chudzinki-Tavassi6Ana Marisa Chudzinki-Tavassi7Luciana Cezar de Cerqueira Leite8Laboratório de Desenvolvimento de Vacinas, Instituto Butantan, São Paulo, BrazilLaboratório de Desenvolvimento de Vacinas, Instituto Butantan, São Paulo, BrazilLaboratório de Desenvolvimento de Vacinas, Instituto Butantan, São Paulo, BrazilLaboratório de Desenvolvimento de Vacinas, Instituto Butantan, São Paulo, BrazilLaboratory Center of Excellence in New Target Discovery (CENTD) Special Laboratory, Instituto Butantan, São Paulo, BrazilCenter of Innovation and Development, Laboratory of Development and Innovation, Instituto Butantan, São Paulo, BrazilLaboratory Center of Excellence in New Target Discovery (CENTD) Special Laboratory, Instituto Butantan, São Paulo, BrazilCenter of Innovation and Development, Laboratory of Development and Innovation, Instituto Butantan, São Paulo, BrazilLaboratório de Desenvolvimento de Vacinas, Instituto Butantan, São Paulo, BrazilTuberculosis (TB) is one of the deadliest infectious diseases around the world. Prevention is based on the prophylactic use of BCG vaccine, effective in infants but as protection wanes with time, adults are less protected. Additionally, chemotherapy requires the use of many antibiotics for several months to be effective. Immunotherapeutic approaches can activate the immune system, intending to assist chemotherapy of TB patients, improving its effectiveness, and reducing treatment time. In this work, the recombinant BCG expressing LTAK63 (rBCG-LTAK63) was evaluated for its immunotherapeutic potential against TB. Bacillary load, immune response, and lung inflammation were evaluated in mice infected with Mycobacterium tuberculosis (Mtb) and treated either with BCG or rBCG-LTAK63 using different routes of administration. Mice infected with Mtb and treated intranasally or intravenously with rBCG-LTAK63 showed a reduced bacillary load and lung inflammatory area when compared to the group treated with BCG. In the spleen, rBCG-LTAK63 administered intravenously induced a higher inflammatory response of CD4+ T cells. On the other hand, in the lungs there was an increased presence of CD4+IL-10+ and regulatory T cells. When combined with a short-term chemotherapy regimen, rBCG-LTAK63 administered subcutaneously or intravenously decreases the Mtb bacillary load, increases the anti-inflammatory response, and reduces tissue inflammation. These findings highlight the potential of rBCG-LTAK63 in assisting chemotherapy against Mtb.https://www.frontiersin.org/articles/10.3389/fimmu.2022.943558/fullBCGtuberculosisrecombinant BCGrBCG-LTAK63immunotherapyimmuno-therapeutic vaccine |
| spellingShingle | Monalisa Martins Trentini Alex Issamu Kanno Dunia Rodriguez Lazaro Moreira Marques-Neto Silas Fernandes Eto Silas Fernandes Eto Ana Marisa Chudzinki-Tavassi Ana Marisa Chudzinki-Tavassi Luciana Cezar de Cerqueira Leite Recombinant BCG expressing the LTAK63 adjuvant improves a short-term chemotherapy schedule in the control of tuberculosis in mice Frontiers in Immunology BCG tuberculosis recombinant BCG rBCG-LTAK63 immunotherapy immuno-therapeutic vaccine |
| title | Recombinant BCG expressing the LTAK63 adjuvant improves a short-term chemotherapy schedule in the control of tuberculosis in mice |
| title_full | Recombinant BCG expressing the LTAK63 adjuvant improves a short-term chemotherapy schedule in the control of tuberculosis in mice |
| title_fullStr | Recombinant BCG expressing the LTAK63 adjuvant improves a short-term chemotherapy schedule in the control of tuberculosis in mice |
| title_full_unstemmed | Recombinant BCG expressing the LTAK63 adjuvant improves a short-term chemotherapy schedule in the control of tuberculosis in mice |
| title_short | Recombinant BCG expressing the LTAK63 adjuvant improves a short-term chemotherapy schedule in the control of tuberculosis in mice |
| title_sort | recombinant bcg expressing the ltak63 adjuvant improves a short term chemotherapy schedule in the control of tuberculosis in mice |
| topic | BCG tuberculosis recombinant BCG rBCG-LTAK63 immunotherapy immuno-therapeutic vaccine |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.943558/full |
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