A1 Journal article (refereed)
A comparative study of the effect of UV and formalin inactivation on the stability and immunogenicity of a Coxsackievirus B1 vaccine (2019)

Hankaniemi, M. M., Stone, V. M., Sioofy-Khojine, A.-B., Heinimäki, S., Marjomäki, V., Hyöty, H., Blazevic, V., Laitinen, O. H., Flodström-Tullberg, M., & Hytönen, V. P. (2019). A comparative study of the effect of UV and formalin inactivation on the stability and immunogenicity of a Coxsackievirus B1 vaccine. Vaccine, 37(40), 5962-5971. https://doi.org/10.1016/j.vaccine.2019.08.037

JYU authors or editors

Publication details

All authors or editors: Hankaniemi, Minna M.; Stone, Virginia M.; Sioofy-Khojine, Amir-Babak; Heinimäki, Suvi; Marjomäki, Varpu; Hyöty, Heikki; Blazevic, Vesna; Laitinen, Olli H.; Flodström-Tullberg, Malin; Hytönen, Vesa P.

Journal or series: Vaccine

ISSN: 0264-410X

eISSN: 1873-2518

Publication year: 2019

Volume: 37

Issue number: 40

Pages range: 5962-5971

Publisher: Elsevier Ltd

Publication country: United Kingdom

Publication language: English

DOI: https://doi.org/10.1016/j.vaccine.2019.08.037

Publication open access: Openly available

Publication channel open access: Partially open access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/65460


Type B Coxsackieviruses (CVBs) belong to the enterovirus genus, and they cause both acute and chronic diseases in humans. CVB infections usually lead to flu-like symptoms but can also result in more serious diseases such as myocarditis, aseptic meningitis and life-threatening multi-organ infections in young infants. Thus, CVBs have long been considered as important targets of future vaccines.

We have previously observed CVB1 capsid disintegration and virus concentration decrease with 12-day long formalin inactivation protocol. Here a scalable ion exchange chromatography purification method was developed, and purified CVB1 was inactivated with UV-C or formalin. Virus morphology and concentration remained unchanged, when the UV (2 min) or formalin (5 days) inactivation were performed in the presence of tween80 detergent. The concentration of the native and UV inactivated CVB1 remained constant at 4 °C during a six months stability study, whereas the concentration of the formalin inactivated vaccine decreased 29% during this time. UV treatment decreased, whereas formalin treatment increased the thermal stability of the capsid.

The formalin inactivated CVB1 vaccine was more immunogenic than the UV inactivated vaccine; the protective neutralizing antibody levels were higher in mice immunized with formalin inactivated vaccine. High levels of CVB1 neutralizing antibodies as well as IgG1 antibodies were detected in mice that were protected against viremia induced by experimental CVB1 infection.

In conclusion, this study describes a scalable ion exchange chromatography purification method and optimized 5-day long formalin inactivation method that preserves CVB1 capsid structure and immunogenicity. Formalin treatment stabilizes the virus particle at elevated temperatures, and the formalin inactivated vaccine induces high levels of serum IgG1 antibodies (Th2 type response) and protective levels of neutralizing antibodies. Formalin inactivated CVB vaccines are promising candidates for human clinical trials.

Keywords: enteroviruses; vaccines; formaldehyde; ultraviolet radiation

Free keywords: coxsackievirus B; inactivated vaccine; formalin; UV

Contributing organizations

Ministry reporting: Yes

Reporting Year: 2019

JUFO rating: 1

Last updated on 2021-14-06 at 13:16