A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
A comparative study of the effect of UV and formalin inactivation on the stability and immunogenicity of a Coxsackievirus B1 vaccine (2019)


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. (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


JYU-tekijät tai -toimittajat


Julkaisun tiedot

Julkaisun kaikki tekijät tai toimittajat: 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.

Lehti tai sarja: Vaccine

ISSN: 0264-410X

eISSN: 1873-2518

Julkaisuvuosi: 2019

Volyymi: 37

Lehden numero: 40

Artikkelin sivunumerot: 5962-5971

Kustantaja: Elsevier Ltd

Julkaisumaa: Britannia

Julkaisun kieli: englanti

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

Avoin saatavuus: Hybridijulkaisukanavassa ilmestynyt avoin julkaisu

Julkaisu on rinnakkaistallennettu (JYX): https://jyx.jyu.fi/handle/123456789/65460


Tiivistelmä

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.


YSO-asiasanat: enterovirukset; rokotteet; formaldehydi; ultraviolettisäteily

Vapaat asiasanat: coxsackievirus B; inactivated vaccine; formalin; UV


Liittyvät organisaatiot


OKM-raportointi: Kyllä

Raportointivuosi: 2019

JUFO-taso: 1


Viimeisin päivitys 2020-18-08 klo 13:24