Heterologous Boosting With Listeria-Based Recombinant Strains in BCG-Primed Mice Improved Protection Against Pulmonary Mycobacterial Infection
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...
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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.02036/full |
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| author | Si-Jing Liu Si-Jing Liu Si-Cheng Tian Si-Cheng Tian Yun-Wen Zhang Yun-Wen Zhang Tian Tang Tian Tang Ju-Mei Zeng Ju-Mei Zeng Xiao-Yong Fan Chuan Wang Chuan Wang |
| author_facet | Si-Jing Liu Si-Jing Liu Si-Cheng Tian Si-Cheng Tian Yun-Wen Zhang Yun-Wen Zhang Tian Tang Tian Tang Ju-Mei Zeng Ju-Mei Zeng Xiao-Yong Fan Chuan Wang Chuan Wang |
| author_sort | Si-Jing Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T23:13:51Z |
| format | Article |
| id | doaj.art-623ec965154a46cfaee4772de3c8c77b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T23:13:51Z |
| publishDate | 2020-09-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-623ec965154a46cfaee4772de3c8c77b2022-12-22T00:08:31ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-09-011110.3389/fimmu.2020.02036558577Heterologous Boosting With Listeria-Based Recombinant Strains in BCG-Primed Mice Improved Protection Against Pulmonary Mycobacterial InfectionSi-Jing Liu0Si-Jing Liu1Si-Cheng Tian2Si-Cheng Tian3Yun-Wen Zhang4Yun-Wen Zhang5Tian Tang6Tian Tang7Ju-Mei Zeng8Ju-Mei Zeng9Xiao-Yong Fan10Chuan Wang11Chuan Wang12West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, ChinaFood Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Department of Public Health Laboratory Sciences, West China School of Public Health, Sichuan University, Chengdu, ChinaWest China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, ChinaFood Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Department of Public Health Laboratory Sciences, West China School of Public Health, Sichuan University, Chengdu, ChinaWest China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, ChinaFood Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Department of Public Health Laboratory Sciences, West China School of Public Health, Sichuan University, Chengdu, ChinaWest China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, ChinaFood Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Department of Public Health Laboratory Sciences, West China School of Public Health, Sichuan University, Chengdu, ChinaWest China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, ChinaFood Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Department of Public Health Laboratory Sciences, West China School of Public Health, Sichuan University, Chengdu, ChinaShanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai, ChinaWest China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, ChinaFood Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Department of Public Health Laboratory Sciences, West China School of Public Health, Sichuan University, Chengdu, ChinaWhile 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.https://www.frontiersin.org/article/10.3389/fimmu.2020.02036/fullMycobacterium tuberculosisvaccineListeria monocytogenesListeria ivanoviimultistage |
| spellingShingle | Si-Jing Liu Si-Jing Liu Si-Cheng Tian Si-Cheng Tian Yun-Wen Zhang Yun-Wen Zhang Tian Tang Tian Tang Ju-Mei Zeng Ju-Mei Zeng Xiao-Yong Fan Chuan Wang Chuan Wang Heterologous Boosting With Listeria-Based Recombinant Strains in BCG-Primed Mice Improved Protection Against Pulmonary Mycobacterial Infection Frontiers in Immunology Mycobacterium tuberculosis vaccine Listeria monocytogenes Listeria ivanovii multistage |
| title | Heterologous Boosting With Listeria-Based Recombinant Strains in BCG-Primed Mice Improved Protection Against Pulmonary Mycobacterial Infection |
| title_full | Heterologous Boosting With Listeria-Based Recombinant Strains in BCG-Primed Mice Improved Protection Against Pulmonary Mycobacterial Infection |
| title_fullStr | Heterologous Boosting With Listeria-Based Recombinant Strains in BCG-Primed Mice Improved Protection Against Pulmonary Mycobacterial Infection |
| title_full_unstemmed | Heterologous Boosting With Listeria-Based Recombinant Strains in BCG-Primed Mice Improved Protection Against Pulmonary Mycobacterial Infection |
| title_short | Heterologous Boosting With Listeria-Based Recombinant Strains in BCG-Primed Mice Improved Protection Against Pulmonary Mycobacterial Infection |
| title_sort | heterologous boosting with listeria based recombinant strains in bcg primed mice improved protection against pulmonary mycobacterial infection |
| topic | Mycobacterium tuberculosis vaccine Listeria monocytogenes Listeria ivanovii multistage |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.02036/full |
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