Cyclic di-AMP as endogenous adjuvant enhanced BCG-induced trained immunity and protection against Mycobacterium tuberculosis in mice
Bacillus Calmette-Guérin (BCG) is a licensed prophylactic vaccine against tuberculosis (TB). Current TB vaccine efforts focus on improving BCG effects through recombination or genetic attenuation and/or boost with different vaccines. Recent years, it was revealed that BCG could elicit non-specific h...
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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.2022.943667/full |
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| author | Huanhuan Ning Jian Kang Yanzhi Lu Xuan Liang Xuan Liang Jie Zhou Rui Ren Shan Zhou Yong Zhao Yanling Xie Yanling Xie Lu Bai Lu Bai Linna Zhang Yali Kang Yali Kang Xiaojing Gao Xiaojing Gao Mingze Xu Yanling Ma Fanglin Zhang Yinlan Bai |
| author_facet | Huanhuan Ning Jian Kang Yanzhi Lu Xuan Liang Xuan Liang Jie Zhou Rui Ren Shan Zhou Yong Zhao Yanling Xie Yanling Xie Lu Bai Lu Bai Linna Zhang Yali Kang Yali Kang Xiaojing Gao Xiaojing Gao Mingze Xu Yanling Ma Fanglin Zhang Yinlan Bai |
| author_sort | Huanhuan Ning |
| collection | DOAJ |
| description | Bacillus Calmette-Guérin (BCG) is a licensed prophylactic vaccine against tuberculosis (TB). Current TB vaccine efforts focus on improving BCG effects through recombination or genetic attenuation and/or boost with different vaccines. Recent years, it was revealed that BCG could elicit non-specific heterogeneous protection against other pathogens such as viruses through a process termed trained immunity. Previously, we constructed a recombinant BCG (rBCG-DisA) with elevated c-di-AMP as endogenous adjuvant by overexpressing di-adenylate cyclase of Mycobacterium tuberculosis DisA, and found that rBCG-DisA induced enhanced immune responses by subcutaneous route in mice after M. tuberculosis infection. In this study, splenocytes from rBCG-DisA immunized mice by intravenous route (i.v) elicited greater proinflammatory cytokine responses to homologous and heterologous re-stimulations than BCG. After M. tuberculosis infection, rBCG-DisA immunized mice showed hallmark responses of trained immunity including potent proinflammatory cytokine responses, enhanced epigenetic changes, altered lncRNA expressions and metabolic rewiring in bone marrow cells and other tissues. Moreover, rBCG-DisA immunization induced higher levels of antibodies and T cells responses in the lung and spleen of mice after M. tuberculosis infection. It was found that rBCG-DisA resided longer than BCG in the lung of M. tuberculosis infected mice implying prolonged duration of vaccine efficacy. Then, we found that rBCG-DisA boosting could prolong survival of BCG-primed mice over 90 weeks against M. tuberculosis infection. Our findings provided in vivo experimental evidence that rBCG-DisA with c-di-AMP as endogenous adjuvant induced enhanced trained immunity and adaptive immunity. What’s more, rBCG-DisA showed promising potential in prime-boost strategy against M. tuberculosis infection in adults. |
| first_indexed | 2024-04-11T21:22:33Z |
| format | Article |
| id | doaj.art-c1d4966480ea44438cff3a523ecfa76b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T21:22:33Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-c1d4966480ea44438cff3a523ecfa76b2022-12-22T04:02:35ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.943667943667Cyclic di-AMP as endogenous adjuvant enhanced BCG-induced trained immunity and protection against Mycobacterium tuberculosis in miceHuanhuan Ning0Jian Kang1Yanzhi Lu2Xuan Liang3Xuan Liang4Jie Zhou5Rui Ren6Shan Zhou7Yong Zhao8Yanling Xie9Yanling Xie10Lu Bai11Lu Bai12Linna Zhang13Yali Kang14Yali Kang15Xiaojing Gao16Xiaojing Gao17Mingze Xu18Yanling Ma19Fanglin Zhang20Yinlan Bai21Department of Microbiology and Pathogen Biology, School of Preclinical Medicine, Air Force Medical University, Xi’an, ChinaDepartment of Microbiology and Pathogen Biology, School of Preclinical Medicine, Air Force Medical University, Xi’an, ChinaDepartment of Microbiology and Pathogen Biology, School of Preclinical Medicine, Air Force Medical University, Xi’an, ChinaDepartment of Microbiology and Pathogen Biology, School of Preclinical Medicine, Air Force Medical University, Xi’an, ChinaCollege of Life Sciences, Northwest University, Xi’an, ChinaDepartment of Endocrinology, Xijing Hospital, Air Force Medical University, Xi’an, ChinaDepartment of Microbiology and Pathogen Biology, School of Preclinical Medicine, Air Force Medical University, Xi’an, ChinaDepartment of Clinical Laboratory, Xijing Hospital, Air Force Medical University, Xi’an, ChinaLaboratory Animal Center, Air Force Medical University, Xi’an, ChinaDepartment of Microbiology and Pathogen Biology, School of Preclinical Medicine, Air Force Medical University, Xi’an, ChinaSchool of Life Sciences, Yan’an University, Yan’an, ChinaDepartment of Microbiology and Pathogen Biology, School of Preclinical Medicine, Air Force Medical University, Xi’an, ChinaSchool of Life Sciences, Yan’an University, Yan’an, ChinaDepartment of Physiology, Basic Medical School, Ningxia Medical University, Yinchuan, ChinaDepartment of Microbiology and Pathogen Biology, School of Preclinical Medicine, Air Force Medical University, Xi’an, ChinaDepartment of Physiology, Basic Medical School, Ningxia Medical University, Yinchuan, ChinaDepartment of Microbiology and Pathogen Biology, School of Preclinical Medicine, Air Force Medical University, Xi’an, ChinaDepartment of Physiology, Basic Medical School, Ningxia Medical University, Yinchuan, ChinaDepartment of Microbiology and Pathogen Biology, School of Preclinical Medicine, Air Force Medical University, Xi’an, ChinaCollege of Life Sciences, Northwest University, Xi’an, ChinaDepartment of Microbiology and Pathogen Biology, School of Preclinical Medicine, Air Force Medical University, Xi’an, ChinaDepartment of Microbiology and Pathogen Biology, School of Preclinical Medicine, Air Force Medical University, Xi’an, ChinaBacillus Calmette-Guérin (BCG) is a licensed prophylactic vaccine against tuberculosis (TB). Current TB vaccine efforts focus on improving BCG effects through recombination or genetic attenuation and/or boost with different vaccines. Recent years, it was revealed that BCG could elicit non-specific heterogeneous protection against other pathogens such as viruses through a process termed trained immunity. Previously, we constructed a recombinant BCG (rBCG-DisA) with elevated c-di-AMP as endogenous adjuvant by overexpressing di-adenylate cyclase of Mycobacterium tuberculosis DisA, and found that rBCG-DisA induced enhanced immune responses by subcutaneous route in mice after M. tuberculosis infection. In this study, splenocytes from rBCG-DisA immunized mice by intravenous route (i.v) elicited greater proinflammatory cytokine responses to homologous and heterologous re-stimulations than BCG. After M. tuberculosis infection, rBCG-DisA immunized mice showed hallmark responses of trained immunity including potent proinflammatory cytokine responses, enhanced epigenetic changes, altered lncRNA expressions and metabolic rewiring in bone marrow cells and other tissues. Moreover, rBCG-DisA immunization induced higher levels of antibodies and T cells responses in the lung and spleen of mice after M. tuberculosis infection. It was found that rBCG-DisA resided longer than BCG in the lung of M. tuberculosis infected mice implying prolonged duration of vaccine efficacy. Then, we found that rBCG-DisA boosting could prolong survival of BCG-primed mice over 90 weeks against M. tuberculosis infection. Our findings provided in vivo experimental evidence that rBCG-DisA with c-di-AMP as endogenous adjuvant induced enhanced trained immunity and adaptive immunity. What’s more, rBCG-DisA showed promising potential in prime-boost strategy against M. tuberculosis infection in adults.https://www.frontiersin.org/articles/10.3389/fimmu.2022.943667/fullBacillus Calmette-Guérincyclic di-AMPtrained immunityadjuvantMycobacterium tuberculosis |
| spellingShingle | Huanhuan Ning Jian Kang Yanzhi Lu Xuan Liang Xuan Liang Jie Zhou Rui Ren Shan Zhou Yong Zhao Yanling Xie Yanling Xie Lu Bai Lu Bai Linna Zhang Yali Kang Yali Kang Xiaojing Gao Xiaojing Gao Mingze Xu Yanling Ma Fanglin Zhang Yinlan Bai Cyclic di-AMP as endogenous adjuvant enhanced BCG-induced trained immunity and protection against Mycobacterium tuberculosis in mice Frontiers in Immunology Bacillus Calmette-Guérin cyclic di-AMP trained immunity adjuvant Mycobacterium tuberculosis |
| title | Cyclic di-AMP as endogenous adjuvant enhanced BCG-induced trained immunity and protection against Mycobacterium tuberculosis in mice |
| title_full | Cyclic di-AMP as endogenous adjuvant enhanced BCG-induced trained immunity and protection against Mycobacterium tuberculosis in mice |
| title_fullStr | Cyclic di-AMP as endogenous adjuvant enhanced BCG-induced trained immunity and protection against Mycobacterium tuberculosis in mice |
| title_full_unstemmed | Cyclic di-AMP as endogenous adjuvant enhanced BCG-induced trained immunity and protection against Mycobacterium tuberculosis in mice |
| title_short | Cyclic di-AMP as endogenous adjuvant enhanced BCG-induced trained immunity and protection against Mycobacterium tuberculosis in mice |
| title_sort | cyclic di amp as endogenous adjuvant enhanced bcg induced trained immunity and protection against mycobacterium tuberculosis in mice |
| topic | Bacillus Calmette-Guérin cyclic di-AMP trained immunity adjuvant Mycobacterium tuberculosis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.943667/full |
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