Large enteroviral vaccination studies to prevent type 1 diabetes should be well founded and rely on scientific evidence. Reply to Skog O, Klingel K, Roivainen M et al [letter]
- 382 Downloads
To the Editor: We are pleased that Skog et al  have accepted the challenge to respond to our recent ‘For Debate’ article . In this, we proposed that both vaccination and trials with antiviral therapies are warranted, based on decades of studies implicating an association between enterovirus infections and type 1 diabetes. It is pleasing to observe these conclusions were similarly supported by Skog et al .
However, while supporting our overall conclusions, the authors also challenged several pieces of evidence cited in our article, and we believe it important to respond to each challenge. First, Skog et al question the value of antiviral therapies at clinical onset of type 1 diabetes because they contend that the evidence for viral infection post diagnosis is weak . In response, we would cite the growing evidence for: (1) chronic autoimmunity and persistent insulin secretion extending for many years after diagnosis [3, 4, 5]; (2) the existence of beta cell dysfunction at...
KeywordsAntiviral agents Clinical trials DiViD Enterovirus Islet nPOD
Protein kinase R
Viral protein 1
All authors were responsible for drafting the article and revising it critically for important intellectual content. All authors approved the version to be published.
Work in the authors’ laboratories is supported by the South-Eastern Norway Regional Health Authority (grant to K.D.-J.), the Novo Nordisk Foundation (grants to KD-J and MF-T), the Swedish Child Diabetes Foundation (grant to MF-T), the Swedish Research Council (grant to MF-T), and by the PEVNET (Persistent Virus Infection in Diabetes Network) Study Group funded by the European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement number 261441 PEVNET. Some of the authors (AP, SJR, NGM, HH, MAA, REL and MF-T) are supported by JDRF 3-SRA-2017-492-A-N, which funds the nPOD Virus Group in collaborative studies of virus infections in the pancreas with type 1 diabetes. Studies in the Exeter laboratory were supported by a JDRF-CDA award (5-CDA-2014-221-A-N to SJR), and by grant support from MRC (MR/P010695/1) and Diabetes UK (15/0005364) to SJR and NGM. MEC is supported by an Australian National Health and Medical Research Council (NHMRC) Practitioner fellowship [APP1045777]
Duality of interest
HH is a shareholder and member of the Board of Vactech Ltd., which develops picornavirus vaccines. RAI, HH and MF-T serve on the scientific advisory board of Provention Bio Inc., which is developing an enterovirus vaccine.
- 1.Skog O, Klingel K, Roivainen M, Korsgren O (2019) Large enteroviral vaccination studies to prevent type 1 diabetes should be well founded and rely on scientific evidence. Diabetologia. https://doi.org/10.1007/s00125-019-4841-1
- 10.Richardson SJ, Leete P, Bone AJ, Foulis AK, Morgan NG (2013) Expression of the enteroviral capsid protein VP1 in the islet cells of patients with type 1 diabetes is associated with induction of protein kinase R and downregulation of Mcl-1. Diabetologia 56(1):185–193. https://doi.org/10.1007/s00125-012-2745-4 CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Richardson SJ, Leete P, Dhayal S et al (2014) Evaluation of the fidelity of immunolabelling obtained with clone 5D8/1, a monoclonal antibody directed against the enteroviral capsid protein, VP1, in human pancreas. Diabetologia 57(2):392–401. https://doi.org/10.1007/s00125-013-3094-7 CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Laiho JE, Oikarinen M, Richardson SJ et al (2016) Relative sensitivity of immunohistochemistry, multiple reaction monitoring mass spectrometry, in situ hybridization and PCR to detect Coxsackievirus B1 in A549 cells. J Clin Virol 77:21–28. https://doi.org/10.1016/j.jcv.2016.01.015 CrossRefPubMedPubMedCentralGoogle Scholar
- 19.Proventionbio (2017) Provention Bio, Inc. Announces clinical program focus on intercepting and preventing the onset of type 1 diabetes. Available from http://investors.proventionbio.com/2017-07-18-Provention-Bio-Inc-Announces-Clinical-Program-Focused-on-Intercepting-and-Preventing-the-Onset-of-Type-1-Diabetes. Accessed 26 March 2019