Coxsackievirus B infections are common in Cystic Fibrosis and experimental evidence supports protection by vaccination
Virginia M. Stone,
Renata Utorova,
Marta Butrym,
Amir-Babak Sioofy-Khojine,
Minna M. Hankaniemi,
Emma E. Ringqvist,
Marfa Blanter,
Anirudra Parajuli,
Terezia Pincikova,
Björn Fischler,
Ferenc Karpati,
Vesa P. Hytönen,
Heikki Hyöty,
Lena Hjelte,
Malin Flodström-Tullberg
Affiliations
Virginia M. Stone
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet and Karolinska University Hospital Huddinge, 141 52 Stockholm, Sweden
Renata Utorova
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet and Karolinska University Hospital Huddinge, 141 52 Stockholm, Sweden
Marta Butrym
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet and Karolinska University Hospital Huddinge, 141 52 Stockholm, Sweden
Amir-Babak Sioofy-Khojine
Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland
Minna M. Hankaniemi
Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland
Emma E. Ringqvist
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet and Karolinska University Hospital Huddinge, 141 52 Stockholm, Sweden
Marfa Blanter
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet and Karolinska University Hospital Huddinge, 141 52 Stockholm, Sweden
Anirudra Parajuli
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet and Karolinska University Hospital Huddinge, 141 52 Stockholm, Sweden
Terezia Pincikova
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet and Karolinska University Hospital Huddinge, 141 52 Stockholm, Sweden; Stockholm CF Center, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden; Division of Pediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet and Department of Pediatrics, Karolinska University Hospital, 141 86 Stockholm, Sweden
Björn Fischler
Division of Pediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet and Department of Pediatrics, Karolinska University Hospital, 141 86 Stockholm, Sweden
Ferenc Karpati
Stockholm CF Center, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden; Division of Pediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet and Department of Pediatrics, Karolinska University Hospital, 141 86 Stockholm, Sweden
Vesa P. Hytönen
Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland; Fimlab Laboratories, 33520 Tampere, Finland
Heikki Hyöty
Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland; Fimlab Laboratories, 33520 Tampere, Finland
Lena Hjelte
Stockholm CF Center, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden; Division of Pediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet and Department of Pediatrics, Karolinska University Hospital, 141 86 Stockholm, Sweden
Malin Flodström-Tullberg
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet and Karolinska University Hospital Huddinge, 141 52 Stockholm, Sweden; Corresponding author
Summary: 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.
