Serotype-Independent Protection Against Invasive Pneumococcal Infections Conferred by Live Vaccine With lgt Deletion
Streptococcus pneumoniae is the most common respiratory bacterial pathogen among cases of community-acquired infection in young children, older adults, and individuals with underlying medical conditions. Although capsular polysaccharide-based pneumococcal vaccines have contributed to significant dec...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01212/full |
| _version_ | 1818512745328279552 |
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| author | A-Yeung Jang A-Yeung Jang Ki Bum Ahn Yong Zhi Yong Zhi Hyun-Jung Ji Hyun-Jung Ji Jing Zhang Seung Hyun Han Huichen Guo Sangyong Lim Sangyong Lim Joon Yong Song Jae Hyang Lim Ho Seong Seo Ho Seong Seo |
| author_facet | A-Yeung Jang A-Yeung Jang Ki Bum Ahn Yong Zhi Yong Zhi Hyun-Jung Ji Hyun-Jung Ji Jing Zhang Seung Hyun Han Huichen Guo Sangyong Lim Sangyong Lim Joon Yong Song Jae Hyang Lim Ho Seong Seo Ho Seong Seo |
| author_sort | A-Yeung Jang |
| collection | DOAJ |
| description | Streptococcus pneumoniae is the most common respiratory bacterial pathogen among cases of community-acquired infection in young children, older adults, and individuals with underlying medical conditions. Although capsular polysaccharide-based pneumococcal vaccines have contributed to significant decrease in invasive pneumococcal infections, these vaccines have some limitations, including limited serotype coverage, lack of effective mucosal antibody responses, and high costs. In this study, we investigated the safety and immunogenicity of a live, whole-cell pneumococcal vaccine constructed by deleting the gene for prolipoprotein diacylglyceryl transferase (lgt) from the encapsulated pneumococcal strain TIGR4 (TIGR4Δlgt) for protection against heterologous pneumococcal strains. Pneumococcal strain TIGR4 was successfully attenuated by deletion of lgt, resulting in the loss of inflammatory activity and virulence. TIGR4Δlgt colonized the nasopharynx long enough to induce strong mucosal IgA and IgG2b-dominant systemic antibody responses that were cross-reactive to heterologous pneumococcal serotypes. Finally, intranasal immunization with TIGR4Δlgt provided serotype-independent protection against pneumococcal challenge in mice. Taken together, our results suggest that TIGR4Δlgt is an avirulent and attractive broad-spectrum pneumococcal vaccine candidate. More broadly, we assert that modulation of such “master” metabolic genes represents an emerging strategy for developing more effective vaccines against numerous infectious agents. |
| first_indexed | 2024-12-10T23:51:22Z |
| format | Article |
| id | doaj.art-848400dc4bb24dd9944487d9b50ae4aa |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T23:51:22Z |
| publishDate | 2019-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-848400dc4bb24dd9944487d9b50ae4aa2022-12-22T01:28:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-05-011010.3389/fimmu.2019.01212448032Serotype-Independent Protection Against Invasive Pneumococcal Infections Conferred by Live Vaccine With lgt DeletionA-Yeung Jang0A-Yeung Jang1Ki Bum Ahn2Yong Zhi3Yong Zhi4Hyun-Jung Ji5Hyun-Jung Ji6Jing Zhang7Seung Hyun Han8Huichen Guo9Sangyong Lim10Sangyong Lim11Joon Yong Song12Jae Hyang Lim13Ho Seong Seo14Ho Seong Seo15Research Division for Biotechnology, Korea Atomic Energy Research Institute, Jeongeup, South KoreaDepartment of Internal Medicine, Korea University College of Medicine, Seoul, South KoreaResearch Division for Biotechnology, Korea Atomic Energy Research Institute, Jeongeup, South KoreaResearch Division for Biotechnology, Korea Atomic Energy Research Institute, Jeongeup, South KoreaDepartment of Radiation Science and Technology, University of Science and Technology, Daejeon, South KoreaResearch Division for Biotechnology, Korea Atomic Energy Research Institute, Jeongeup, South KoreaDRI and BK21 Plus Program, Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, Seoul, South KoreaResearch Division for Biotechnology, Korea Atomic Energy Research Institute, Jeongeup, South KoreaDRI and BK21 Plus Program, Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, Seoul, South KoreaState Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaResearch Division for Biotechnology, Korea Atomic Energy Research Institute, Jeongeup, South KoreaDepartment of Radiation Science and Technology, University of Science and Technology, Daejeon, South KoreaDepartment of Internal Medicine, Korea University College of Medicine, Seoul, South KoreaDepartment of Microbiology, Ewha Womans University College of Medicine, Seoul, South KoreaResearch Division for Biotechnology, Korea Atomic Energy Research Institute, Jeongeup, South KoreaDepartment of Radiation Science and Technology, University of Science and Technology, Daejeon, South KoreaStreptococcus pneumoniae is the most common respiratory bacterial pathogen among cases of community-acquired infection in young children, older adults, and individuals with underlying medical conditions. Although capsular polysaccharide-based pneumococcal vaccines have contributed to significant decrease in invasive pneumococcal infections, these vaccines have some limitations, including limited serotype coverage, lack of effective mucosal antibody responses, and high costs. In this study, we investigated the safety and immunogenicity of a live, whole-cell pneumococcal vaccine constructed by deleting the gene for prolipoprotein diacylglyceryl transferase (lgt) from the encapsulated pneumococcal strain TIGR4 (TIGR4Δlgt) for protection against heterologous pneumococcal strains. Pneumococcal strain TIGR4 was successfully attenuated by deletion of lgt, resulting in the loss of inflammatory activity and virulence. TIGR4Δlgt colonized the nasopharynx long enough to induce strong mucosal IgA and IgG2b-dominant systemic antibody responses that were cross-reactive to heterologous pneumococcal serotypes. Finally, intranasal immunization with TIGR4Δlgt provided serotype-independent protection against pneumococcal challenge in mice. Taken together, our results suggest that TIGR4Δlgt is an avirulent and attractive broad-spectrum pneumococcal vaccine candidate. More broadly, we assert that modulation of such “master” metabolic genes represents an emerging strategy for developing more effective vaccines against numerous infectious agents.https://www.frontiersin.org/article/10.3389/fimmu.2019.01212/fullStreptococcus pneumoniaeLgtlipoproteinlive attenuated vaccinemucosal immunity |
| spellingShingle | A-Yeung Jang A-Yeung Jang Ki Bum Ahn Yong Zhi Yong Zhi Hyun-Jung Ji Hyun-Jung Ji Jing Zhang Seung Hyun Han Huichen Guo Sangyong Lim Sangyong Lim Joon Yong Song Jae Hyang Lim Ho Seong Seo Ho Seong Seo Serotype-Independent Protection Against Invasive Pneumococcal Infections Conferred by Live Vaccine With lgt Deletion Frontiers in Immunology Streptococcus pneumoniae Lgt lipoprotein live attenuated vaccine mucosal immunity |
| title | Serotype-Independent Protection Against Invasive Pneumococcal Infections Conferred by Live Vaccine With lgt Deletion |
| title_full | Serotype-Independent Protection Against Invasive Pneumococcal Infections Conferred by Live Vaccine With lgt Deletion |
| title_fullStr | Serotype-Independent Protection Against Invasive Pneumococcal Infections Conferred by Live Vaccine With lgt Deletion |
| title_full_unstemmed | Serotype-Independent Protection Against Invasive Pneumococcal Infections Conferred by Live Vaccine With lgt Deletion |
| title_short | Serotype-Independent Protection Against Invasive Pneumococcal Infections Conferred by Live Vaccine With lgt Deletion |
| title_sort | serotype independent protection against invasive pneumococcal infections conferred by live vaccine with lgt deletion |
| topic | Streptococcus pneumoniae Lgt lipoprotein live attenuated vaccine mucosal immunity |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01212/full |
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