Protection against tuberculosis achieved by dissolving microneedle patches loaded with live Mycobacterium paragordonae in a BCG prime-boost strategy
IntroductionSkin vaccination using dissolving microneedle patch (MNP) technology for transdermal delivery is a promising vaccine delivery strategy to overcome the limitations of the existing vaccine administration strategies using syringes. To improve the traditional microneedle mold fabrication tec...
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1178688/full |
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| author | Mi-Hyun Lee Mi-Hyun Lee Mi-Hyun Lee Hyejun Seo Hyejun Seo Hyejun Seo Moon-Su Lee Byoung Jun Kim Hye Lin Kim Hye Lin Kim Du Hyung Lee Du Hyung Lee Jaehun Oh Jaehun Oh Jaehun Oh Ju Yeop Shin Ju Young Jin Do Hyeon Jeong Bum-Joon Kim Bum-Joon Kim Bum-Joon Kim Bum-Joon Kim Bum-Joon Kim Bum-Joon Kim |
| author_facet | Mi-Hyun Lee Mi-Hyun Lee Mi-Hyun Lee Hyejun Seo Hyejun Seo Hyejun Seo Moon-Su Lee Byoung Jun Kim Hye Lin Kim Hye Lin Kim Du Hyung Lee Du Hyung Lee Jaehun Oh Jaehun Oh Jaehun Oh Ju Yeop Shin Ju Young Jin Do Hyeon Jeong Bum-Joon Kim Bum-Joon Kim Bum-Joon Kim Bum-Joon Kim Bum-Joon Kim Bum-Joon Kim |
| author_sort | Mi-Hyun Lee |
| collection | DOAJ |
| description | IntroductionSkin vaccination using dissolving microneedle patch (MNP) technology for transdermal delivery is a promising vaccine delivery strategy to overcome the limitations of the existing vaccine administration strategies using syringes. To improve the traditional microneedle mold fabrication technique, we introduced droplet extension (DEN) to reduce drug loss. Tuberculosis remains a major public health problem worldwide, and BCG revaccination had failed to increase the protective efficacy against tuberculosis. We developed an MNP with live Mycobacterium paragordonae (Mpg) (Mpg-MNP) as a candidate of tuberculosis booster vaccine in a heterologous prime-boost strategy to increase the BCG vaccine efficacy.Materials and methodsThe MNPs were fabricated by the DEN method on a polyvinyl alcohol mask film and hydrocolloid-adhesive sheet with microneedles composed of a mixture of mycobacteria and hyaluronic acid. We assessed the transdermal delivery efficiency by comparing the activation of the dermal immune system with that of subcutaneous injection. A BCG prime Mpg-MNP boost regimen was administered to a mouse model to evaluate the protective efficacy against M. tuberculosis.ResultsWe demonstrated the successful transdermal delivery achieved by Mpg-MNP compared with that observed with BCG-MNP or subcutaneous vaccination via an increased abundance of MHCII-expressing Langerin+ cells within the dermis that could migrate into draining lymph nodes to induce T-cell activation. In a BCG prime-boost regimen, Mpg-MNP was more protective than BCG-only immunization or BCG-MNP boost, resulting in a lower bacterial burden in the lungs of mice infected with virulent M. tuberculosis. Mpg-MNP-boosted mice showed higher serum levels of IgG than BCG-MNP-boosted mice. Furthermore, Ag85B-specific T-cells were activated after BCG priming and Mpg-MNP boost, indicating increased production of Th1-related cytokines in response to M. tuberculosis challenge, which is correlated with enhanced protective efficacy.DiscussionThe MNP fabricated by the DEN method maintained the viability of Mpg and achieved effective release in the dermis. Our data demonstrate a potential application of Mpg-MNP as a booster vaccine to enhance the efficacy of BCG vaccination against M. tuberculosis. This study produced the first MNP loaded with nontuberculous mycobacteria (NTM) to be used as a heterologous booster vaccine with verified protective efficacy against M. tuberculosis. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-c8fc58c68b174757943d1fc3be4df90e2023-06-16T05:42:58ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-06-011410.3389/fimmu.2023.11786881178688Protection against tuberculosis achieved by dissolving microneedle patches loaded with live Mycobacterium paragordonae in a BCG prime-boost strategyMi-Hyun Lee0Mi-Hyun Lee1Mi-Hyun Lee2Hyejun Seo3Hyejun Seo4Hyejun Seo5Moon-Su Lee6Byoung Jun Kim7Hye Lin Kim8Hye Lin Kim9Du Hyung Lee10Du Hyung Lee11Jaehun Oh12Jaehun Oh13Jaehun Oh14Ju Yeop Shin15Ju Young Jin16Do Hyeon Jeong17Bum-Joon Kim18Bum-Joon Kim19Bum-Joon Kim20Bum-Joon Kim21Bum-Joon Kim22Bum-Joon Kim23Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Republic of KoreaDepartment of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of KoreaBK21 FOUR Biomedical Science Project, Seoul National University College of Medicine, Seoul, Republic of KoreaDepartment of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Republic of KoreaCancer Research Institute, College of Medicine, Seoul National University, Seoul, Republic of KoreaInstitute of Endemic Diseases, Seoul National University Medical Research Center (SNUMRC), Seoul, Republic of KoreaMedical Business Division, Raphas Co., Ltd., Seoul, Republic of KoreaDepartment of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Republic of KoreaDepartment of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Republic of KoreaCancer Research Institute, College of Medicine, Seoul National University, Seoul, Republic of KoreaDepartment of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Republic of KoreaCancer Research Institute, College of Medicine, Seoul National University, Seoul, Republic of KoreaDepartment of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Republic of KoreaDepartment of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of KoreaBK21 FOUR Biomedical Science Project, Seoul National University College of Medicine, Seoul, Republic of KoreaMedical Business Division, Raphas Co., Ltd., Seoul, Republic of KoreaMedical Business Division, Raphas Co., Ltd., Seoul, Republic of KoreaMedical Business Division, Raphas Co., Ltd., Seoul, Republic of KoreaDepartment of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Republic of KoreaDepartment of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of KoreaBK21 FOUR Biomedical Science Project, Seoul National University College of Medicine, Seoul, Republic of KoreaCancer Research Institute, College of Medicine, Seoul National University, Seoul, Republic of KoreaInstitute of Endemic Diseases, Seoul National University Medical Research Center (SNUMRC), Seoul, Republic of KoreaLiver Research Institute, College of Medicine, Seoul National University, Seoul, Republic of KoreaIntroductionSkin vaccination using dissolving microneedle patch (MNP) technology for transdermal delivery is a promising vaccine delivery strategy to overcome the limitations of the existing vaccine administration strategies using syringes. To improve the traditional microneedle mold fabrication technique, we introduced droplet extension (DEN) to reduce drug loss. Tuberculosis remains a major public health problem worldwide, and BCG revaccination had failed to increase the protective efficacy against tuberculosis. We developed an MNP with live Mycobacterium paragordonae (Mpg) (Mpg-MNP) as a candidate of tuberculosis booster vaccine in a heterologous prime-boost strategy to increase the BCG vaccine efficacy.Materials and methodsThe MNPs were fabricated by the DEN method on a polyvinyl alcohol mask film and hydrocolloid-adhesive sheet with microneedles composed of a mixture of mycobacteria and hyaluronic acid. We assessed the transdermal delivery efficiency by comparing the activation of the dermal immune system with that of subcutaneous injection. A BCG prime Mpg-MNP boost regimen was administered to a mouse model to evaluate the protective efficacy against M. tuberculosis.ResultsWe demonstrated the successful transdermal delivery achieved by Mpg-MNP compared with that observed with BCG-MNP or subcutaneous vaccination via an increased abundance of MHCII-expressing Langerin+ cells within the dermis that could migrate into draining lymph nodes to induce T-cell activation. In a BCG prime-boost regimen, Mpg-MNP was more protective than BCG-only immunization or BCG-MNP boost, resulting in a lower bacterial burden in the lungs of mice infected with virulent M. tuberculosis. Mpg-MNP-boosted mice showed higher serum levels of IgG than BCG-MNP-boosted mice. Furthermore, Ag85B-specific T-cells were activated after BCG priming and Mpg-MNP boost, indicating increased production of Th1-related cytokines in response to M. tuberculosis challenge, which is correlated with enhanced protective efficacy.DiscussionThe MNP fabricated by the DEN method maintained the viability of Mpg and achieved effective release in the dermis. Our data demonstrate a potential application of Mpg-MNP as a booster vaccine to enhance the efficacy of BCG vaccination against M. tuberculosis. This study produced the first MNP loaded with nontuberculous mycobacteria (NTM) to be used as a heterologous booster vaccine with verified protective efficacy against M. tuberculosis.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1178688/fullMycobacterium tuberculosisMycobacterium paragordonaemicroneedle patchBCG booster vaccinedroplet extension method |
| spellingShingle | Mi-Hyun Lee Mi-Hyun Lee Mi-Hyun Lee Hyejun Seo Hyejun Seo Hyejun Seo Moon-Su Lee Byoung Jun Kim Hye Lin Kim Hye Lin Kim Du Hyung Lee Du Hyung Lee Jaehun Oh Jaehun Oh Jaehun Oh Ju Yeop Shin Ju Young Jin Do Hyeon Jeong Bum-Joon Kim Bum-Joon Kim Bum-Joon Kim Bum-Joon Kim Bum-Joon Kim Bum-Joon Kim Protection against tuberculosis achieved by dissolving microneedle patches loaded with live Mycobacterium paragordonae in a BCG prime-boost strategy Frontiers in Immunology Mycobacterium tuberculosis Mycobacterium paragordonae microneedle patch BCG booster vaccine droplet extension method |
| title | Protection against tuberculosis achieved by dissolving microneedle patches loaded with live Mycobacterium paragordonae in a BCG prime-boost strategy |
| title_full | Protection against tuberculosis achieved by dissolving microneedle patches loaded with live Mycobacterium paragordonae in a BCG prime-boost strategy |
| title_fullStr | Protection against tuberculosis achieved by dissolving microneedle patches loaded with live Mycobacterium paragordonae in a BCG prime-boost strategy |
| title_full_unstemmed | Protection against tuberculosis achieved by dissolving microneedle patches loaded with live Mycobacterium paragordonae in a BCG prime-boost strategy |
| title_short | Protection against tuberculosis achieved by dissolving microneedle patches loaded with live Mycobacterium paragordonae in a BCG prime-boost strategy |
| title_sort | protection against tuberculosis achieved by dissolving microneedle patches loaded with live mycobacterium paragordonae in a bcg prime boost strategy |
| topic | Mycobacterium tuberculosis Mycobacterium paragordonae microneedle patch BCG booster vaccine droplet extension method |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1178688/full |
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