Self-assembling Gn head ferritin nanoparticle vaccine provides full protection from lethal challenge of Dabie bandavirus in aged ferrets
ABSTRACT Dabie bandavirus (DBV), previously known as severe fever with thrombocytopenia syndrome (SFTS) virus, induces a characteristic thrombocytopenia with a mortality rate ranging from 12% to as high as 30%. The sero-prevalence of DBV in healthy people is not significantly different among age gro...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-10-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.01868-23 |
| _version_ | 1827150302319476736 |
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| author | Dokyun Kim Eunha Kim Semi Kim Youseung Chung Chih-Jen Lai Inho Cha Sung-Dong Cho Yunseo Choi Xinghong Dai Stephanie Kim Seokmin Kang Mi-Jeong Kwak Ziyi Liu Younho Choi Su-Hyung Park Young Ki Choi Jae U. Jung |
| author_facet | Dokyun Kim Eunha Kim Semi Kim Youseung Chung Chih-Jen Lai Inho Cha Sung-Dong Cho Yunseo Choi Xinghong Dai Stephanie Kim Seokmin Kang Mi-Jeong Kwak Ziyi Liu Younho Choi Su-Hyung Park Young Ki Choi Jae U. Jung |
| author_sort | Dokyun Kim |
| collection | DOAJ |
| description | ABSTRACT Dabie bandavirus (DBV), previously known as severe fever with thrombocytopenia syndrome (SFTS) virus, induces a characteristic thrombocytopenia with a mortality rate ranging from 12% to as high as 30%. The sero-prevalence of DBV in healthy people is not significantly different among age groups, but clinically diagnosed SFTS patients are older than ~50 years, suggesting that age is the critical risk factor for SFTS morbidity and mortality. Accordingly, our immune-competent ferret model demonstrates an age (4 years old)-dependent DBV infection and pathogenesis that fully recapitulates human clinical manifestation. To protect the aged population from DBV-induced SFTS, vaccine should carry robust immunogenicity with high safety profile. Previous studies have shown that glycoproteins Gn/Gc are the most effective antigens to induce both neutralizing antibody (NAb)- and T-cell-mediated immunity for full protection from DBV infection. Here, we report the development of a protein subunit vaccine with 24-mer self-assembling ferritin (FT) nanoparticle to present the DBV Gn head region (GnH) to enhance immunogenicity. Anion exchange chromatography and size exclusion chromatography readily purified the GnH-FT nanoparticles to homogeneity with structural integrity. Mice immunized with GnH-FT nanoparticles induced robust NAb response and T-cell immunity against DBV Gn. Furthermore, aged ferrets immunized with GnH-FT nanoparticles were fully protected from DBV challenge without SFTS symptoms such as body weight loss, thrombocytopenia, leukopenia, and fatality. This study demonstrates that DBV GnH-FT nanoparticles provide an efficient vaccine efficacy in mouse and aged ferret models and should be an outstanding vaccine candidate targeted for the aged population against fatal DBV infection. IMPORTANCE Dabie bandavirus (DBV) is an emerging tick-borne virus that causes severe fever with thrombocytopenia syndrome (SFTS) in infected patients. Human SFTS symptoms progress from fever, fatigue, and muscle pain to the depletion of white blood cells and platelets with fatality rates up to 30%. The recent spread of its vector tick to over 20 states in the United States increases the potential for outbreaks of the SFTS beyond the East Asia. Thus, the development of vaccine to control this rapidly emerging virus is a high priority. In this study, we applied self-assembling ferritin (FT) nanoparticle to enhance the immunogenicity of DBV Gn head domain (GnH) as a vaccine target. Mice immunized with the GnH-FT nanoparticle vaccine induced potent antibody responses and cellular immunity. Immunized aged ferrets were fully protected from the lethal challenge of DBV. Our study describes the GnH-FT nanoparticle vaccine candidate that provides protective immunity against the emerging DBV infection. |
| first_indexed | 2024-03-11T08:30:23Z |
| format | Article |
| id | doaj.art-6081eecbaf4b4ea0952b801b20c85d73 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2025-03-20T21:31:55Z |
| publishDate | 2023-10-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-6081eecbaf4b4ea0952b801b20c85d732024-08-11T18:20:45ZengAmerican Society for MicrobiologymBio2150-75112023-10-0114510.1128/mbio.01868-23Self-assembling Gn head ferritin nanoparticle vaccine provides full protection from lethal challenge of Dabie bandavirus in aged ferretsDokyun Kim0Eunha Kim1Semi Kim2Youseung Chung3Chih-Jen Lai4Inho Cha5Sung-Dong Cho6Yunseo Choi7Xinghong Dai8Stephanie Kim9Seokmin Kang10Mi-Jeong Kwak11Ziyi Liu12Younho Choi13Su-Hyung Park14Young Ki Choi15Jae U. Jung16Department of Cancer Biology, Infection Biology Program, and Global Center for Pathogen and Human Health Research, Lerner Research Institute, Cleveland Clinic , Cleveland, Ohio, USACollege of Medicine and Medical Research Institute, Chungbuk National University , Cheongju, Republic of KoreaCollege of Medicine and Medical Research Institute, Chungbuk National University , Cheongju, Republic of KoreaGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology , Daejeon, Republic of KoreaDepartment of Cancer Biology, Infection Biology Program, and Global Center for Pathogen and Human Health Research, Lerner Research Institute, Cleveland Clinic , Cleveland, Ohio, USADepartment of Cancer Biology, Infection Biology Program, and Global Center for Pathogen and Human Health Research, Lerner Research Institute, Cleveland Clinic , Cleveland, Ohio, USAGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology , Daejeon, Republic of KoreaGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology , Daejeon, Republic of KoreaDepartment of Physiology and Biophysics, Case Western Reserve University , Cleveland, Ohio, USADepartment of Cancer Biology, Infection Biology Program, and Global Center for Pathogen and Human Health Research, Lerner Research Institute, Cleveland Clinic , Cleveland, Ohio, USADepartment of Cancer Biology, Infection Biology Program, and Global Center for Pathogen and Human Health Research, Lerner Research Institute, Cleveland Clinic , Cleveland, Ohio, USADepartment of Cancer Biology, Infection Biology Program, and Global Center for Pathogen and Human Health Research, Lerner Research Institute, Cleveland Clinic , Cleveland, Ohio, USADepartment of Cancer Biology, Infection Biology Program, and Global Center for Pathogen and Human Health Research, Lerner Research Institute, Cleveland Clinic , Cleveland, Ohio, USAFlorida Research and Innovation Center, Cleveland Clinic , Port St. Lucie, Florida, USAGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology , Daejeon, Republic of KoreaCollege of Medicine and Medical Research Institute, Chungbuk National University , Cheongju, Republic of KoreaDepartment of Cancer Biology, Infection Biology Program, and Global Center for Pathogen and Human Health Research, Lerner Research Institute, Cleveland Clinic , Cleveland, Ohio, USAABSTRACT Dabie bandavirus (DBV), previously known as severe fever with thrombocytopenia syndrome (SFTS) virus, induces a characteristic thrombocytopenia with a mortality rate ranging from 12% to as high as 30%. The sero-prevalence of DBV in healthy people is not significantly different among age groups, but clinically diagnosed SFTS patients are older than ~50 years, suggesting that age is the critical risk factor for SFTS morbidity and mortality. Accordingly, our immune-competent ferret model demonstrates an age (4 years old)-dependent DBV infection and pathogenesis that fully recapitulates human clinical manifestation. To protect the aged population from DBV-induced SFTS, vaccine should carry robust immunogenicity with high safety profile. Previous studies have shown that glycoproteins Gn/Gc are the most effective antigens to induce both neutralizing antibody (NAb)- and T-cell-mediated immunity for full protection from DBV infection. Here, we report the development of a protein subunit vaccine with 24-mer self-assembling ferritin (FT) nanoparticle to present the DBV Gn head region (GnH) to enhance immunogenicity. Anion exchange chromatography and size exclusion chromatography readily purified the GnH-FT nanoparticles to homogeneity with structural integrity. Mice immunized with GnH-FT nanoparticles induced robust NAb response and T-cell immunity against DBV Gn. Furthermore, aged ferrets immunized with GnH-FT nanoparticles were fully protected from DBV challenge without SFTS symptoms such as body weight loss, thrombocytopenia, leukopenia, and fatality. This study demonstrates that DBV GnH-FT nanoparticles provide an efficient vaccine efficacy in mouse and aged ferret models and should be an outstanding vaccine candidate targeted for the aged population against fatal DBV infection. IMPORTANCE Dabie bandavirus (DBV) is an emerging tick-borne virus that causes severe fever with thrombocytopenia syndrome (SFTS) in infected patients. Human SFTS symptoms progress from fever, fatigue, and muscle pain to the depletion of white blood cells and platelets with fatality rates up to 30%. The recent spread of its vector tick to over 20 states in the United States increases the potential for outbreaks of the SFTS beyond the East Asia. Thus, the development of vaccine to control this rapidly emerging virus is a high priority. In this study, we applied self-assembling ferritin (FT) nanoparticle to enhance the immunogenicity of DBV Gn head domain (GnH) as a vaccine target. Mice immunized with the GnH-FT nanoparticle vaccine induced potent antibody responses and cellular immunity. Immunized aged ferrets were fully protected from the lethal challenge of DBV. Our study describes the GnH-FT nanoparticle vaccine candidate that provides protective immunity against the emerging DBV infection.https://journals.asm.org/doi/10.1128/mbio.01868-23Dabie bandavirusnanoparticletick-borne pathogensvaccineferret model |
| spellingShingle | Dokyun Kim Eunha Kim Semi Kim Youseung Chung Chih-Jen Lai Inho Cha Sung-Dong Cho Yunseo Choi Xinghong Dai Stephanie Kim Seokmin Kang Mi-Jeong Kwak Ziyi Liu Younho Choi Su-Hyung Park Young Ki Choi Jae U. Jung Self-assembling Gn head ferritin nanoparticle vaccine provides full protection from lethal challenge of Dabie bandavirus in aged ferrets mBio Dabie bandavirus nanoparticle tick-borne pathogens vaccine ferret model |
| title | Self-assembling Gn head ferritin nanoparticle vaccine provides full protection from lethal challenge of Dabie bandavirus in aged ferrets |
| title_full | Self-assembling Gn head ferritin nanoparticle vaccine provides full protection from lethal challenge of Dabie bandavirus in aged ferrets |
| title_fullStr | Self-assembling Gn head ferritin nanoparticle vaccine provides full protection from lethal challenge of Dabie bandavirus in aged ferrets |
| title_full_unstemmed | Self-assembling Gn head ferritin nanoparticle vaccine provides full protection from lethal challenge of Dabie bandavirus in aged ferrets |
| title_short | Self-assembling Gn head ferritin nanoparticle vaccine provides full protection from lethal challenge of Dabie bandavirus in aged ferrets |
| title_sort | self assembling gn head ferritin nanoparticle vaccine provides full protection from lethal challenge of dabie bandavirus in aged ferrets |
| topic | Dabie bandavirus nanoparticle tick-borne pathogens vaccine ferret model |
| url | https://journals.asm.org/doi/10.1128/mbio.01868-23 |
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