Structural Insight into CVB3-VLP Non-Adjuvanted Vaccine
Coxsackievirus B (CVB) enteroviruses are common pathogens that can cause acute and chronic myocarditis, dilated cardiomyopathy, aseptic meningitis, and they are hypothesized to be a causal factor in type 1 diabetes. The licensed enterovirus vaccines and those currently in clinical development are tr...
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doaj-2ce670a6a010445b87d452f5a9fe7e9e2020-11-25T03:51:32ZengMDPI AGMicroorganisms2076-26072020-08-0181287128710.3390/microorganisms8091287Structural Insight into CVB3-VLP Non-Adjuvanted VaccineMinna M. Hankaniemi0Mo A. Baikoghli1Virginia M. Stone2Li Xing3Outi Väätäinen4Saana Soppela5Amirbabak Sioofy-Khojine6Niila V. V. Saarinen7Tingwei Ou8Brandon Anson9Heikki Hyöty10Varpu Marjomäki11Malin Flodström-Tullberg12R. Holland Cheng13Vesa P. Hytönen14Olli H. Laitinen15Faculty of Medicine and Life Sciences, Tampere University, FI-33014 Tampere, FinlandDepartment of Molecular and Cellular Biology, University of California, Davis, CA 95616, USAThe Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, SE-141 52 Stockholm, SwedenDepartment of Molecular and Cellular Biology, University of California, Davis, CA 95616, USAFaculty of Medicine and Life Sciences, Tampere University, FI-33014 Tampere, FinlandFaculty of Medicine and Life Sciences, Tampere University, FI-33014 Tampere, FinlandFaculty of Medicine and Life Sciences, Tampere University, FI-33014 Tampere, FinlandFaculty of Medicine and Life Sciences, Tampere University, FI-33014 Tampere, FinlandDepartment of Molecular and Cellular Biology, University of California, Davis, CA 95616, USADepartment of Molecular and Cellular Biology, University of California, Davis, CA 95616, USAFaculty of Medicine and Life Sciences, Tampere University, FI-33014 Tampere, FinlandDepartment of Biological and Environmental Science/Nanoscience Center, University of Jyväskylä, P.O. Box 35, FI-40014 Jyväskylä, FinlandThe Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, SE-141 52 Stockholm, SwedenDepartment of Molecular and Cellular Biology, University of California, Davis, CA 95616, USAFaculty of Medicine and Life Sciences, Tampere University, FI-33014 Tampere, FinlandFaculty of Medicine and Life Sciences, Tampere University, FI-33014 Tampere, FinlandCoxsackievirus B (CVB) enteroviruses are common pathogens that can cause acute and chronic myocarditis, dilated cardiomyopathy, aseptic meningitis, and they are hypothesized to be a causal factor in type 1 diabetes. The licensed enterovirus vaccines and those currently in clinical development are traditional inactivated or live attenuated vaccines. Even though these vaccines work well in the prevention of enterovirus diseases, new vaccine technologies, like virus-like particles (VLPs), can offer important advantages in the manufacturing and epitope engineering. We have previously produced VLPs for CVB3 and CVB1 in insect cells. Here, we describe the production of CVB3-VLPs with enhanced production yield and purity using an improved purification method consisting of tangential flow filtration and ion exchange chromatography, which is compatible with industrial scale production. We also resolved the CVB3-VLP structure by Cryo-Electron Microscopy imaging and single particle reconstruction. The VLP diameter is 30.9 nm on average, and it is similar to Coxsackievirus A VLPs and the expanded enterovirus cell-entry intermediate (the 135s particle), which is ~2 nm larger than the mature virion. High neutralizing and total IgG antibody levels, the latter being a predominantly Th2 type (IgG1) phenotype, were detected in C57BL/6J mice immunized with non-adjuvanted CVB3-VLP vaccine. The structural and immunogenic data presented here indicate the potential of this improved methodology to produce highly immunogenic enterovirus VLP-vaccines in the future.https://www.mdpi.com/2076-2607/8/9/1287Coxsackievirus B (CVB)vaccinevirus-like particle (VLP) |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Minna M. Hankaniemi Mo A. Baikoghli Virginia M. Stone Li Xing Outi Väätäinen Saana Soppela Amirbabak Sioofy-Khojine Niila V. V. Saarinen Tingwei Ou Brandon Anson Heikki Hyöty Varpu Marjomäki Malin Flodström-Tullberg R. Holland Cheng Vesa P. Hytönen Olli H. Laitinen |
spellingShingle |
Minna M. Hankaniemi Mo A. Baikoghli Virginia M. Stone Li Xing Outi Väätäinen Saana Soppela Amirbabak Sioofy-Khojine Niila V. V. Saarinen Tingwei Ou Brandon Anson Heikki Hyöty Varpu Marjomäki Malin Flodström-Tullberg R. Holland Cheng Vesa P. Hytönen Olli H. Laitinen Structural Insight into CVB3-VLP Non-Adjuvanted Vaccine Microorganisms Coxsackievirus B (CVB) vaccine virus-like particle (VLP) |
author_facet |
Minna M. Hankaniemi Mo A. Baikoghli Virginia M. Stone Li Xing Outi Väätäinen Saana Soppela Amirbabak Sioofy-Khojine Niila V. V. Saarinen Tingwei Ou Brandon Anson Heikki Hyöty Varpu Marjomäki Malin Flodström-Tullberg R. Holland Cheng Vesa P. Hytönen Olli H. Laitinen |
author_sort |
Minna M. Hankaniemi |
title |
Structural Insight into CVB3-VLP Non-Adjuvanted Vaccine |
title_short |
Structural Insight into CVB3-VLP Non-Adjuvanted Vaccine |
title_full |
Structural Insight into CVB3-VLP Non-Adjuvanted Vaccine |
title_fullStr |
Structural Insight into CVB3-VLP Non-Adjuvanted Vaccine |
title_full_unstemmed |
Structural Insight into CVB3-VLP Non-Adjuvanted Vaccine |
title_sort |
structural insight into cvb3-vlp non-adjuvanted vaccine |
publisher |
MDPI AG |
series |
Microorganisms |
issn |
2076-2607 |
publishDate |
2020-08-01 |
description |
Coxsackievirus B (CVB) enteroviruses are common pathogens that can cause acute and chronic myocarditis, dilated cardiomyopathy, aseptic meningitis, and they are hypothesized to be a causal factor in type 1 diabetes. The licensed enterovirus vaccines and those currently in clinical development are traditional inactivated or live attenuated vaccines. Even though these vaccines work well in the prevention of enterovirus diseases, new vaccine technologies, like virus-like particles (VLPs), can offer important advantages in the manufacturing and epitope engineering. We have previously produced VLPs for CVB3 and CVB1 in insect cells. Here, we describe the production of CVB3-VLPs with enhanced production yield and purity using an improved purification method consisting of tangential flow filtration and ion exchange chromatography, which is compatible with industrial scale production. We also resolved the CVB3-VLP structure by Cryo-Electron Microscopy imaging and single particle reconstruction. The VLP diameter is 30.9 nm on average, and it is similar to Coxsackievirus A VLPs and the expanded enterovirus cell-entry intermediate (the 135s particle), which is ~2 nm larger than the mature virion. High neutralizing and total IgG antibody levels, the latter being a predominantly Th2 type (IgG1) phenotype, were detected in C57BL/6J mice immunized with non-adjuvanted CVB3-VLP vaccine. The structural and immunogenic data presented here indicate the potential of this improved methodology to produce highly immunogenic enterovirus VLP-vaccines in the future. |
topic |
Coxsackievirus B (CVB) vaccine virus-like particle (VLP) |
url |
https://www.mdpi.com/2076-2607/8/9/1287 |
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