A1 Journal article (refereed)
Structural Insight into CVB3-VLP Non-Adjuvanted Vaccine (2020)

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, 8(9), Article 1287. https://doi.org/10.3390/microorganisms8091287

JYU authors or editors

Publication details

All authors or editors: 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; et al.

Journal or series: Microorganisms

eISSN: 2076-2607

Publication year: 2020

Volume: 8

Issue number: 9

Article number: 1287

Publisher: MDPI

Publication country: Switzerland

Publication language: English

DOI: https://doi.org/10.3390/microorganisms8091287

Publication open access: Openly available

Publication channel open access: Open Access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/71670

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 ~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.

Keywords: enteroviruses; vaccines

Free keywords: Coxsackievirus B (CVB); vaccine; virus-like particle (VLP)

Contributing organizations

Ministry reporting: Yes

Reporting Year: 2020

JUFO rating: 1