Structural Insight into CVB3-VLP Non-Adjuvanted Vaccine

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http://hdl.handle.net/10138/321118

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Hankaniemi , M M , Baikoghli , M A , Stone , V M , Xing , L , Väätäinen , O , Soppela , S , Sioofy-Khojine , A , Saarinen , N V V , Ou , T , Anson , B , Hyöty , H , Marjomäki , V , Flodström-Tullberg , M , Cheng , R H , Hytönen , V P & Laitinen , O H 2020 , ' Structural Insight into CVB3-VLP Non-Adjuvanted Vaccine ' , Microorganisms , vol. 8 , no. 9 , 1287 . https://doi.org/10.3390/microorganisms8091287

Title: Structural Insight into CVB3-VLP Non-Adjuvanted Vaccine
Author: Hankaniemi, Minna M.; Baikoghli, Mo A.; Stone, Virginia M.; Xing, Li; Väätäinen, Outi; Soppela, Saana; Sioofy-Khojine, Amirbabak; Saarinen, Niila V. V.; Ou, Tingwei; Anson, Brandon; Hyöty, Heikki; Marjomäki, Varpu; Flodström-Tullberg, Malin; Cheng, R. Holland; Hytönen, Vesa P.; Laitinen, Olli H.
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
Date: 2020-09
Language: eng
Number of pages: 13
Belongs to series: Microorganisms
ISSN: 2076-2607
URI: http://hdl.handle.net/10138/321118
Abstract: 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.
Subject: Coxsackievirus B (CVB)
vaccine
virus-like particle (VLP)
COXSACKIEVIRUS B3
ENTEROVIRUS 71
PARTICLE VACCINE
RECEPTOR-BINDING
IMMUNE-RESPONSE
PROTECTS MICE
VIRUS
MICROSCOPY
POLIOVIRUS
B1
11832 Microbiology and virology
3111 Biomedicine
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