BAFF and APRIL immunotherapy following Bacille Calmette-Guérin vaccination enhances protection against pulmonary tuberculosis in mice
IntroductionBacille Calmette-Guérin (BCG), the only tuberculosis vaccine currently in clinical use, provides inadequate long-term protection. Administered at birth, BCG induces broad immune responses against a large number of antigens shared with Mycobacterium tuberculosis (Mtb), but protection wane...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1551183/full |
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| author | Min Xie Chen-Yu Tsai Joshua Woo Frank Nuritdinov Melissa Cristaldo Narineh M. Odjourian Rosleine Antilus-Sainte Maureen Dougher Martin Gengenbacher Martin Gengenbacher |
| author_facet | Min Xie Chen-Yu Tsai Joshua Woo Frank Nuritdinov Melissa Cristaldo Narineh M. Odjourian Rosleine Antilus-Sainte Maureen Dougher Martin Gengenbacher Martin Gengenbacher |
| author_sort | Min Xie |
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| description | IntroductionBacille Calmette-Guérin (BCG), the only tuberculosis vaccine currently in clinical use, provides inadequate long-term protection. Administered at birth, BCG induces broad immune responses against a large number of antigens shared with Mycobacterium tuberculosis (Mtb), but protection wanes over time. We have previously shown that unconventional B cell subsets play a role in tuberculosis control.MethodsHigh-dimensional flow cytometry and multiplex cytokine analysis were employed to investigate the effects of immunotherapy on BCG-vaccinated mice in an Mtb challenge model.ResultsIn this study, we investigate the potential of recombinant cytokines targeting B cells – B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL) – to modulate BCG immunity and improve protection in mice. Both cytokines play overlapping roles in B cell development and peripheral survival. Following subcutaneous BCG vaccination, immunotherapy with BAFF or APRIL resulted in an increased frequency of unconventional B cells potentially transitioning into antibody-producing plasma cells. Concurrently, we observed an increased frequency of central memory T cells, a subset critical for protective immunity. Changes in cellular immune responses were accompanied by reduced pro-inflammatory cytokine profiles and a contraction of the leukocyte population in lungs. Importantly, mice receiving BCG vaccination followed by BAFF or APRIL immunotherapy exhibited superior long-term protection against pulmonary tuberculosis relative to controls that received only BCG.ConclusionIn summary, our findings demonstrate that combining BCG vaccination with B cell targeted immunomodulatory therapies can improve long-term protection against pulmonary tuberculosis, highlighting the continued relevance and underutilized potential of BCG as a vaccine platform. |
| format | Article |
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| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-f1d2755eb8784942a603c44a90fa0bc82025-02-06T07:10:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15511831551183BAFF and APRIL immunotherapy following Bacille Calmette-Guérin vaccination enhances protection against pulmonary tuberculosis in miceMin Xie0Chen-Yu Tsai1Joshua Woo2Frank Nuritdinov3Melissa Cristaldo4Narineh M. Odjourian5Rosleine Antilus-Sainte6Maureen Dougher7Martin Gengenbacher8Martin Gengenbacher9Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, United StatesCenter for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, United StatesCenter for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, United StatesCenter for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, United StatesCenter for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, United StatesCenter for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, United StatesCenter for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, United StatesCenter for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, United StatesCenter for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, United StatesDepartment of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, NJ, United StatesIntroductionBacille Calmette-Guérin (BCG), the only tuberculosis vaccine currently in clinical use, provides inadequate long-term protection. Administered at birth, BCG induces broad immune responses against a large number of antigens shared with Mycobacterium tuberculosis (Mtb), but protection wanes over time. We have previously shown that unconventional B cell subsets play a role in tuberculosis control.MethodsHigh-dimensional flow cytometry and multiplex cytokine analysis were employed to investigate the effects of immunotherapy on BCG-vaccinated mice in an Mtb challenge model.ResultsIn this study, we investigate the potential of recombinant cytokines targeting B cells – B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL) – to modulate BCG immunity and improve protection in mice. Both cytokines play overlapping roles in B cell development and peripheral survival. Following subcutaneous BCG vaccination, immunotherapy with BAFF or APRIL resulted in an increased frequency of unconventional B cells potentially transitioning into antibody-producing plasma cells. Concurrently, we observed an increased frequency of central memory T cells, a subset critical for protective immunity. Changes in cellular immune responses were accompanied by reduced pro-inflammatory cytokine profiles and a contraction of the leukocyte population in lungs. Importantly, mice receiving BCG vaccination followed by BAFF or APRIL immunotherapy exhibited superior long-term protection against pulmonary tuberculosis relative to controls that received only BCG.ConclusionIn summary, our findings demonstrate that combining BCG vaccination with B cell targeted immunomodulatory therapies can improve long-term protection against pulmonary tuberculosis, highlighting the continued relevance and underutilized potential of BCG as a vaccine platform.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1551183/fullBCGunconventional B cellsmarginal-zone B cellsimmunotherapymemory T cellsmycobacterium tuberculosis |
| spellingShingle | Min Xie Chen-Yu Tsai Joshua Woo Frank Nuritdinov Melissa Cristaldo Narineh M. Odjourian Rosleine Antilus-Sainte Maureen Dougher Martin Gengenbacher Martin Gengenbacher BAFF and APRIL immunotherapy following Bacille Calmette-Guérin vaccination enhances protection against pulmonary tuberculosis in mice Frontiers in Immunology BCG unconventional B cells marginal-zone B cells immunotherapy memory T cells mycobacterium tuberculosis |
| title | BAFF and APRIL immunotherapy following Bacille Calmette-Guérin vaccination enhances protection against pulmonary tuberculosis in mice |
| title_full | BAFF and APRIL immunotherapy following Bacille Calmette-Guérin vaccination enhances protection against pulmonary tuberculosis in mice |
| title_fullStr | BAFF and APRIL immunotherapy following Bacille Calmette-Guérin vaccination enhances protection against pulmonary tuberculosis in mice |
| title_full_unstemmed | BAFF and APRIL immunotherapy following Bacille Calmette-Guérin vaccination enhances protection against pulmonary tuberculosis in mice |
| title_short | BAFF and APRIL immunotherapy following Bacille Calmette-Guérin vaccination enhances protection against pulmonary tuberculosis in mice |
| title_sort | baff and april immunotherapy following bacille calmette guerin vaccination enhances protection against pulmonary tuberculosis in mice |
| topic | BCG unconventional B cells marginal-zone B cells immunotherapy memory T cells mycobacterium tuberculosis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1551183/full |
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