Journal
MICROORGANISMS
Volume 8, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/microorganisms8091287
Keywords
Coxsackievirus B (CVB); vaccine; virus-like particle (VLP)
Categories
Funding
- Academy of Finland [309455, 266492]
- Business Finland [THERDIAB 1843/31/2014]
- FiDiPro grant NOVAC [1913/31/2012]
- Strategic Research Program in Diabetes at Karolinska Institutet
- Swedish Child Diabetes Foundation
- Swedish Medical Research Council [2017-02020]
- Business Finland (FiDiPro grant) [1913/31/2012]
- National Institute of Food and Agriculture
- National Institutes of Health [AI095382, EB021230, CA198880]
- Swedish Research Council [2017-02020] Funding Source: Swedish Research Council
- Academy of Finland (AKA) [309455, 309455] Funding Source: Academy of Finland (AKA)
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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 similar to 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.
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