TY - JOUR
T1 - Coxsackievirus B infections are common in Cystic Fibrosis and experimental evidence supports protection by vaccination
AU - Stone, Virginia M.
AU - Utorova, Renata
AU - Butrym, Marta
AU - Sioofy-Khojine, Amir Babak
AU - Hankaniemi, Minna M.
AU - Ringqvist, Emma E.
AU - Blanter, Marfa
AU - Parajuli, Anirudra
AU - Pincikova, Terezia
AU - Fischler, Björn
AU - Karpati, Ferenc
AU - Hytönen, Vesa P.
AU - Hyöty, Heikki
AU - Hjelte, Lena
AU - Flodström-Tullberg, Malin
N1 - Funding Information:
We would like to thank the research nurses at the Stockholm CF Center, staff at the pre-clinical laboratory (PKL) at the Karolinska Institute, and staff at the Faculty of Medicine and Health Technology (University of Tampere) for assistance. We also thank Dr. B. Scholte, University of Rotterdam, The Netherlands, for sharing the Cftr tm1EUR mouse model. Drs K. Blom, J. Michaelsson, and J.K. Sandberg. Karolinska Institutet are greatly acknowledged for sharing serum samples from healthy control individuals. We also thank S. Parvin, Karolinska Institute, for her technical help with processing and staining histological samples and the members of the Flodström-Tullberg group for discussion and critical feedback on the study. We acknowledge Biocenter Finland and the Karolinska University Hospital for infrastructure support. Finally, we would like to thank the healthy controls and individuals with CF involved in the study for their participation. The graphical abstract was created using BioRender.com . This work has been supported by grants awarded by The Swedish Heart-Lung Foundation (grants 20170764 and 20200682 awarded to M.F.T.), The Swedish Research Council (grant 2020-02969 ; MFT), Erica Lederhausens Minnesstiftelse (grant/award number not applicable; M.F.T.), The Swedish Child Diabetes Foundation (grant/award number not applicable; M.F.T. and V.M.S.), Karolinska Institute including the Strategic Research Program in Diabetes (M.F.T.) and Clinical Training Program (R.U.), Riksförbundet Cystisk Fibros (grant/award number not applicable; M.F.T.), Business Finland (formerly TEKES; THERDIAB project, diary no. 1843/31/2014 ), the Academy of Finland (grants 288671 and 309455 awarded to H.H. and M.M.H., respectively), and the Sigrid Jusélius Foundation grant (grant/award number not applicable; H.H.).
Funding Information:
We would like to thank the research nurses at the Stockholm CF Center, staff at the pre-clinical laboratory (PKL) at the Karolinska Institute, and staff at the Faculty of Medicine and Health Technology (University of Tampere) for assistance. We also thank Dr. B. Scholte, University of Rotterdam, The Netherlands, for sharing the Cftrtm1EUR mouse model. Drs K. Blom, J. Michaelsson, and J.K. Sandberg. Karolinska Institutet are greatly acknowledged for sharing serum samples from healthy control individuals. We also thank S. Parvin, Karolinska Institute, for her technical help with processing and staining histological samples and the members of the Flodström-Tullberg group for discussion and critical feedback on the study. We acknowledge Biocenter Finland and the Karolinska University Hospital for infrastructure support. Finally, we would like to thank the healthy controls and individuals with CF involved in the study for their participation. The graphical abstract was created using BioRender.com. This work has been supported by grants awarded by The Swedish Heart-Lung Foundation (grants 20170764 and 20200682 awarded to M.F.T.), The Swedish Research Council (grant 2020-02969; MFT), Erica Lederhausens Minnesstiftelse (grant/award number not applicable; M.F.T.), The Swedish Child Diabetes Foundation (grant/award number not applicable; M.F.T. and V.M.S.), Karolinska Institute including the Strategic Research Program in Diabetes (M.F.T.) and Clinical Training Program (R.U.), Riksförbundet Cystisk Fibros (grant/award number not applicable; M.F.T.), Business Finland (formerly TEKES; THERDIAB project, diary no. 1843/31/2014), the Academy of Finland (grants 288671 and 309455 awarded to H.H. and M.M.H. respectively), and the Sigrid Jusélius Foundation grant (grant/award number not applicable; H.H.). Conceptualization: V.M.S. R.U. T.P. F.K. B.F. H.H. L.H. and M.F.T.; methodology: V.M.S. R.U. M.B. A.B.S.K. M.M.H. E.E.R. M.B. and A.P.; formal analysis: V.M.S. R.U. M.B. E.E.R. A.B.S.K. and M.F.T.; investigation and resources: V.M.S. R.U. M.B. A.B.S.K. M.M.H. E.E.R. M.B. and M.F.T.; writing – original draft preparation: V.M.S. R.U. M.B. and M.F.T.; writing – review and editing: V.M.S. R.U. M.B. A.B.S.K. M.M.H. E.E.R. M.B. A.P. T.P. B.F. F.K. V.P.H. H.H. L.H. M.F.T.; supervision: B.F. F.K. V.P.H. H.H. L.H. and M.F.T.; funding acquisition: M.M.H. V.P.H. H.H. L.H. and M.F.T. H.H. owns stocks in, and is the chairman of, the board of Vactech Ltd that develops vaccines against picornaviruses. H.H. and M.F.T. serve on the scientific advisory board of Provention Bio Inc. that develops vaccines against Coxsackie B viruses in collaboration with Vactech Ltd. The remaining authors declare that they have no conflict of interests.
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/10/21
Y1 - 2022/10/21
N2 - Viral respiratory tract infections exacerbate airway disease and facilitate life-threatening bacterial colonization in cystic fibrosis (CF). Annual influenza vaccination is recommended and vaccines against other common respiratory viruses may further reduce pulmonary morbidity risk. Enteroviruses have been found in nasopharyngeal samples from CF patients experiencing pulmonary exacerbations. Using serology tests, we found that infections by a group of enteroviruses, Coxsackievirus Bs (CVBs), are prevalent in CF. We next showed that a CVB vaccine, currently undergoing clinical development, prevents infection and CVB-instigated lung damage in a murine model of CF. Finally, we demonstrate that individuals with CF have normal vaccine responses to a similar, commonly used enterovirus vaccine (inactivated poliovirus vaccine). Our study demonstrates that CVB infections are common in CF and provides experimental evidence indicating that CVB vaccines could be efficacious in the CF population. The role of CVB infections in contributing to pulmonary exacerbations in CF should be further studied.
AB - Viral respiratory tract infections exacerbate airway disease and facilitate life-threatening bacterial colonization in cystic fibrosis (CF). Annual influenza vaccination is recommended and vaccines against other common respiratory viruses may further reduce pulmonary morbidity risk. Enteroviruses have been found in nasopharyngeal samples from CF patients experiencing pulmonary exacerbations. Using serology tests, we found that infections by a group of enteroviruses, Coxsackievirus Bs (CVBs), are prevalent in CF. We next showed that a CVB vaccine, currently undergoing clinical development, prevents infection and CVB-instigated lung damage in a murine model of CF. Finally, we demonstrate that individuals with CF have normal vaccine responses to a similar, commonly used enterovirus vaccine (inactivated poliovirus vaccine). Our study demonstrates that CVB infections are common in CF and provides experimental evidence indicating that CVB vaccines could be efficacious in the CF population. The role of CVB infections in contributing to pulmonary exacerbations in CF should be further studied.
KW - Virology
U2 - 10.1016/j.isci.2022.105070
DO - 10.1016/j.isci.2022.105070
M3 - Article
AN - SCOPUS:85138105898
SN - 2589-0042
VL - 25
JO - Iscience
JF - Iscience
IS - 10
M1 - 105070
ER -