Heterologous Boosting With Listeria-Based Recombinant Strains in BCG-Primed Mice Improved Protection Against Pulmonary Mycobacterial Infection
Copyright © 2020 Liu, Tian, Zhang, Tang, Zeng, Fan and Wang..
While Baccillus Calmette-Guerin (BCG) is used worldwide, tuberculosis (TB) is still a global concern due to the poor efficacy of BCG. Novel vaccine candidates are therefore urgently required. In this study, two attenuated recombinant Listeria strains, LMΔ-msv and LIΔ-msv were constructed by deletion of actA and plcB and expression of a fusion protein consisting of T cell epitopes from four Mycobacterium tuberculosis (Mtb) antigens (Rv2460c, Rv2660c, Rv3875, and Rv3804c). The safety and immunogenicity of the two recombinant strains were evaluated in C57BL/6J mice. After intravenous immunization individually, both recombinant strains entered liver and spleen but eventually were eliminated from these organs after several days. Simultaneously, they induced antigen-specific cell-mediated immunity, indicating that the recombinant Listeria strains were immunogenic and safe in vivo. LMΔ-msv immunization induced stronger cellular immune responses than LIΔ-msv immunization, and when boosted with LIΔ-msv, antigen-specific IFN-γ CD8+ T cell responses were notably magnified. Furthermore, we evaluated the protection conferred by the vaccine candidates against mycobacterial infection via challenging the mice with 1 × 107 CFU of BCG. Especially, we tested the feasibility of application of them as heterologous BCG supplement vaccine by immunization of mice with BCG firstly, and boosted with LMΔ-msv and LIΔ-msv sequentially before challenging. Combination immune strategy (LMΔ-msv prime-LIΔ-msv boost) conferred comparable protection efficacy as BCG alone. More importantly, BCG-vaccinated mice acquired stronger resistance to Mycobacterial challenge when boosted with LMΔ-msv and LIΔ-msv sequentially. Our results inferred that heterologous immunization with Listeria-based recombinant strains boosted BCG-primed protection against pulmonary mycobacterial infection.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Frontiers in immunology - 11(2020) vom: 18., Seite 2036 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Si-Jing [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.04.2021 Date Revised 22.04.2021 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.3389/fimmu.2020.02036 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM315538694 |
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| 245 | 1 | 0 | |a Heterologous Boosting With Listeria-Based Recombinant Strains in BCG-Primed Mice Improved Protection Against Pulmonary Mycobacterial Infection |
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| 520 | |a Copyright © 2020 Liu, Tian, Zhang, Tang, Zeng, Fan and Wang. | ||
| 520 | |a While Baccillus Calmette-Guerin (BCG) is used worldwide, tuberculosis (TB) is still a global concern due to the poor efficacy of BCG. Novel vaccine candidates are therefore urgently required. In this study, two attenuated recombinant Listeria strains, LMΔ-msv and LIΔ-msv were constructed by deletion of actA and plcB and expression of a fusion protein consisting of T cell epitopes from four Mycobacterium tuberculosis (Mtb) antigens (Rv2460c, Rv2660c, Rv3875, and Rv3804c). The safety and immunogenicity of the two recombinant strains were evaluated in C57BL/6J mice. After intravenous immunization individually, both recombinant strains entered liver and spleen but eventually were eliminated from these organs after several days. Simultaneously, they induced antigen-specific cell-mediated immunity, indicating that the recombinant Listeria strains were immunogenic and safe in vivo. LMΔ-msv immunization induced stronger cellular immune responses than LIΔ-msv immunization, and when boosted with LIΔ-msv, antigen-specific IFN-γ CD8+ T cell responses were notably magnified. Furthermore, we evaluated the protection conferred by the vaccine candidates against mycobacterial infection via challenging the mice with 1 × 107 CFU of BCG. Especially, we tested the feasibility of application of them as heterologous BCG supplement vaccine by immunization of mice with BCG firstly, and boosted with LMΔ-msv and LIΔ-msv sequentially before challenging. Combination immune strategy (LMΔ-msv prime-LIΔ-msv boost) conferred comparable protection efficacy as BCG alone. More importantly, BCG-vaccinated mice acquired stronger resistance to Mycobacterial challenge when boosted with LMΔ-msv and LIΔ-msv sequentially. Our results inferred that heterologous immunization with Listeria-based recombinant strains boosted BCG-primed protection against pulmonary mycobacterial infection | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Listeria ivanovii | |
| 650 | 4 | |a Listeria monocytogenes | |
| 650 | 4 | |a Mycobacterium tuberculosis | |
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| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a Immunoglobulin G |2 NLM | |
| 650 | 7 | |a Tuberculosis Vaccines |2 NLM | |
| 700 | 1 | |a Tian, Si-Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yun-Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Tian |e verfasserin |4 aut | |
| 700 | 1 | |a Zeng, Ju-Mei |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Xiao-Yong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Chuan |e verfasserin |4 aut | |
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