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dc.contributor.authorHankaniemi, Minna M.
dc.contributor.authorStone, Virginia M.
dc.contributor.authorSioofy-Khojine, Amir-Babak
dc.contributor.authorHeinimäki, Suvi
dc.contributor.authorMarjomäki, Varpu
dc.contributor.authorHyöty, Heikki
dc.contributor.authorBlazevic, Vesna
dc.contributor.authorLaitinen, Olli H.
dc.contributor.authorFlodström-Tullberg, Malin
dc.contributor.authorHytönen, Vesa P.
dc.date.accessioned2019-09-09T11:05:27Z
dc.date.available2019-09-09T11:05:27Z
dc.date.issued2019
dc.identifier.citationHankaniemi, 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. (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. DOI: 10.1016/j.vaccine.2019.08.037
dc.identifier.otherCONVID_32509939
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/65460
dc.description.abstractType 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.en
dc.format.mimetypeapplication/pdf
dc.languageeng
dc.publisherElsevier Ltd
dc.relation.ispartofseriesVaccine
dc.rightsCC BY 4.0
dc.subject.othercoxsackievirus B
dc.subject.otherinactivated vaccine
dc.subject.otherformalin
dc.subject.otherUV
dc.titleA comparative study of the effect of UV and formalin inactivation on the stability and immunogenicity of a Coxsackievirus B1 vaccine
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-201909094060
dc.contributor.laitosBio- ja ympäristötieteiden laitosfi
dc.contributor.laitosDepartment of Biological and Environmental Scienceen
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.description.reviewstatuspeerReviewed
dc.format.pagerange5962-5971
dc.relation.issn0264-410X
dc.relation.numberinseries40
dc.relation.volume37
dc.type.versionpublishedVersion
dc.rights.copyright© 2019 The Author(s).
dc.rights.accesslevelopenAccessfi
dc.subject.ysorokotteet
dc.subject.ysoformaldehydi
dc.subject.ysoultraviolettisäteily
dc.subject.ysoenterovirukset
dc.format.contentfulltext
jyx.subject.urihttp://www.yso.fi/onto/yso/p15634
jyx.subject.urihttp://www.yso.fi/onto/yso/p16085
jyx.subject.urihttp://www.yso.fi/onto/yso/p18200
jyx.subject.urihttp://www.yso.fi/onto/yso/p20689
dc.rights.urlhttps://creativecommons.org/licenses/by/4.0/
dc.relation.doi10.1016/j.vaccine.2019.08.037
jyx.fundinginformationThe research was funded by the Academy of Finland (projects 1309455 and 288671), Business Finland (project HERDIAB: 1843/31/2014), the Swedish Child Diabetes Foundation, Karolinska Institutet including the Strategic Research Program in Diabetes and Jane and Aatos Erkko Foundation.


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