B21 DNA vaccine expressing ag85b, rv2029c, and rv1738 confers a robust therapeutic effect against latent Mycobacterium tuberculosis infection
Latent tuberculosis infection (LTBI) treatment is known to accelerate the decline in TB incidence, especially in high-risk populations. Mycobacterium tuberculosis (M. tb) expression profiles differ at different growth periods, and vaccines protective and therapeutic effects may increase when they in...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-12-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1025931/full |
| _version_ | 1811310491231846400 |
|---|---|
| author | Shufeng Weng Jinyi Zhang Huixia Ma Jingyu Zhou Liqiu Jia Yanmin Wan Yanmin Wan Peng Cui Peng Cui Qiaoling Ruan Lingyun Shao Jing Wu Honghai Wang Wenhong Zhang Wenhong Zhang Wenhong Zhang Ying Xu Ying Xu |
| author_facet | Shufeng Weng Jinyi Zhang Huixia Ma Jingyu Zhou Liqiu Jia Yanmin Wan Yanmin Wan Peng Cui Peng Cui Qiaoling Ruan Lingyun Shao Jing Wu Honghai Wang Wenhong Zhang Wenhong Zhang Wenhong Zhang Ying Xu Ying Xu |
| author_sort | Shufeng Weng |
| collection | DOAJ |
| description | Latent tuberculosis infection (LTBI) treatment is known to accelerate the decline in TB incidence, especially in high-risk populations. Mycobacterium tuberculosis (M. tb) expression profiles differ at different growth periods, and vaccines protective and therapeutic effects may increase when they include antigenic compositions from different periods. To develop a post-exposure vaccine that targets LTBI, we constructed four therapeutic DNA vaccines (A39, B37, B31, and B21) using different combinations of antigens from the proliferation phase (Ag85A, Ag85B), PE/PPE family (Rv3425), and latent phase (Rv2029c, Rv1813c, Rv1738). We compared the immunogenicity of the four DNA vaccines in C57BL/6j mice. The B21 vaccine stimulated the strongest cellular immune responses, namely Th1/Th17 and CD8+ cytotoxic T lymphocyte responses. It also induced the generation of strengthened effector memory and central memory T cells. In latently infected mice, the B21 vaccine significantly reduced bacterial loads in the spleens and lungs and decreased lung pathology. In conclusion, the B21 DNA vaccine can enhance T cell responses and control the reactivation of LTBI. |
| first_indexed | 2024-04-13T09:59:45Z |
| format | Article |
| id | doaj.art-9ea2758ef7914736bebd9e58efd68469 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T09:59:45Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9ea2758ef7914736bebd9e58efd684692022-12-22T02:51:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-12-011310.3389/fimmu.2022.10259311025931B21 DNA vaccine expressing ag85b, rv2029c, and rv1738 confers a robust therapeutic effect against latent Mycobacterium tuberculosis infectionShufeng Weng0Jinyi Zhang1Huixia Ma2Jingyu Zhou3Liqiu Jia4Yanmin Wan5Yanmin Wan6Peng Cui7Peng Cui8Qiaoling Ruan9Lingyun Shao10Jing Wu11Honghai Wang12Wenhong Zhang13Wenhong Zhang14Wenhong Zhang15Ying Xu16Ying Xu17State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, ChinaState Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, ChinaState Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, ChinaDepartment of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, ChinaState Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, ChinaDepartment of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, ChinaState Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, ChinaDepartment of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, ChinaState Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, ChinaDepartment of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, ChinaNational Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, ChinaKey Laboratory of Medical Molecular Virology (MOE/MOH), Shanghai Medical College, Fudan University, Shanghai, ChinaState Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, ChinaShanghai Huashen Institute of Microbes and Infections, Shanghai, ChinaLatent tuberculosis infection (LTBI) treatment is known to accelerate the decline in TB incidence, especially in high-risk populations. Mycobacterium tuberculosis (M. tb) expression profiles differ at different growth periods, and vaccines protective and therapeutic effects may increase when they include antigenic compositions from different periods. To develop a post-exposure vaccine that targets LTBI, we constructed four therapeutic DNA vaccines (A39, B37, B31, and B21) using different combinations of antigens from the proliferation phase (Ag85A, Ag85B), PE/PPE family (Rv3425), and latent phase (Rv2029c, Rv1813c, Rv1738). We compared the immunogenicity of the four DNA vaccines in C57BL/6j mice. The B21 vaccine stimulated the strongest cellular immune responses, namely Th1/Th17 and CD8+ cytotoxic T lymphocyte responses. It also induced the generation of strengthened effector memory and central memory T cells. In latently infected mice, the B21 vaccine significantly reduced bacterial loads in the spleens and lungs and decreased lung pathology. In conclusion, the B21 DNA vaccine can enhance T cell responses and control the reactivation of LTBI.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1025931/fullDNA vaccineimmunotherapyMycobacterium tuberculosisLTBIB21 DNA |
| spellingShingle | Shufeng Weng Jinyi Zhang Huixia Ma Jingyu Zhou Liqiu Jia Yanmin Wan Yanmin Wan Peng Cui Peng Cui Qiaoling Ruan Lingyun Shao Jing Wu Honghai Wang Wenhong Zhang Wenhong Zhang Wenhong Zhang Ying Xu Ying Xu B21 DNA vaccine expressing ag85b, rv2029c, and rv1738 confers a robust therapeutic effect against latent Mycobacterium tuberculosis infection Frontiers in Immunology DNA vaccine immunotherapy Mycobacterium tuberculosis LTBI B21 DNA |
| title | B21 DNA vaccine expressing ag85b, rv2029c, and rv1738 confers a robust therapeutic effect against latent Mycobacterium tuberculosis infection |
| title_full | B21 DNA vaccine expressing ag85b, rv2029c, and rv1738 confers a robust therapeutic effect against latent Mycobacterium tuberculosis infection |
| title_fullStr | B21 DNA vaccine expressing ag85b, rv2029c, and rv1738 confers a robust therapeutic effect against latent Mycobacterium tuberculosis infection |
| title_full_unstemmed | B21 DNA vaccine expressing ag85b, rv2029c, and rv1738 confers a robust therapeutic effect against latent Mycobacterium tuberculosis infection |
| title_short | B21 DNA vaccine expressing ag85b, rv2029c, and rv1738 confers a robust therapeutic effect against latent Mycobacterium tuberculosis infection |
| title_sort | b21 dna vaccine expressing ag85b rv2029c and rv1738 confers a robust therapeutic effect against latent mycobacterium tuberculosis infection |
| topic | DNA vaccine immunotherapy Mycobacterium tuberculosis LTBI B21 DNA |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1025931/full |
| work_keys_str_mv | AT shufengweng b21dnavaccineexpressingag85brv2029candrv1738confersarobusttherapeuticeffectagainstlatentmycobacteriumtuberculosisinfection AT jinyizhang b21dnavaccineexpressingag85brv2029candrv1738confersarobusttherapeuticeffectagainstlatentmycobacteriumtuberculosisinfection AT huixiama b21dnavaccineexpressingag85brv2029candrv1738confersarobusttherapeuticeffectagainstlatentmycobacteriumtuberculosisinfection AT jingyuzhou b21dnavaccineexpressingag85brv2029candrv1738confersarobusttherapeuticeffectagainstlatentmycobacteriumtuberculosisinfection AT liqiujia b21dnavaccineexpressingag85brv2029candrv1738confersarobusttherapeuticeffectagainstlatentmycobacteriumtuberculosisinfection AT yanminwan b21dnavaccineexpressingag85brv2029candrv1738confersarobusttherapeuticeffectagainstlatentmycobacteriumtuberculosisinfection AT yanminwan b21dnavaccineexpressingag85brv2029candrv1738confersarobusttherapeuticeffectagainstlatentmycobacteriumtuberculosisinfection AT pengcui b21dnavaccineexpressingag85brv2029candrv1738confersarobusttherapeuticeffectagainstlatentmycobacteriumtuberculosisinfection AT pengcui b21dnavaccineexpressingag85brv2029candrv1738confersarobusttherapeuticeffectagainstlatentmycobacteriumtuberculosisinfection AT qiaolingruan b21dnavaccineexpressingag85brv2029candrv1738confersarobusttherapeuticeffectagainstlatentmycobacteriumtuberculosisinfection AT lingyunshao b21dnavaccineexpressingag85brv2029candrv1738confersarobusttherapeuticeffectagainstlatentmycobacteriumtuberculosisinfection AT jingwu b21dnavaccineexpressingag85brv2029candrv1738confersarobusttherapeuticeffectagainstlatentmycobacteriumtuberculosisinfection AT honghaiwang b21dnavaccineexpressingag85brv2029candrv1738confersarobusttherapeuticeffectagainstlatentmycobacteriumtuberculosisinfection AT wenhongzhang b21dnavaccineexpressingag85brv2029candrv1738confersarobusttherapeuticeffectagainstlatentmycobacteriumtuberculosisinfection AT wenhongzhang b21dnavaccineexpressingag85brv2029candrv1738confersarobusttherapeuticeffectagainstlatentmycobacteriumtuberculosisinfection AT wenhongzhang b21dnavaccineexpressingag85brv2029candrv1738confersarobusttherapeuticeffectagainstlatentmycobacteriumtuberculosisinfection AT yingxu b21dnavaccineexpressingag85brv2029candrv1738confersarobusttherapeuticeffectagainstlatentmycobacteriumtuberculosisinfection AT yingxu b21dnavaccineexpressingag85brv2029candrv1738confersarobusttherapeuticeffectagainstlatentmycobacteriumtuberculosisinfection |