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Diabetologia
Published in: Diabetologia 2/2015

01-02-2015 | Article

A preclinical study on the efficacy and safety of a new vaccine against Coxsackievirus B1 reveals no risk for accelerated diabetes development in mouse models

Authors: Pär G. Larsson, Tadepally Lakshmikanth, Olli H. Laitinen, Renata Utorova, Stella Jacobson, Maarit Oikarinen, Erna Domsgen, Minni R. L. Koivunen, Pascal Chaux, Nicolas Devard, Valerie Lecouturier, Jeffrey Almond, Mikael Knip, Heikki Hyöty, Malin Flodström-Tullberg

Published in: Diabetologia | Issue 2/2015

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Abstract

Aims/hypothesis

Enterovirus infections have been implicated in the aetiology of autoimmune type 1 diabetes. A vaccine could be used to test the causal relationship between enterovirus infections and diabetes development. However, the development of a vaccine against a virus suspected to induce an autoimmune disease is challenging, since the vaccine itself might trigger autoimmunity. Another challenge is to select the enterovirus serotypes to target with a vaccine. Here we aimed to evaluate the function and autoimmune safety of a novel non-adjuvanted prototype vaccine to Coxsackievirus serotype B1 (CVB1), a member of the enterovirus genus.

Methods

A formalin-inactivated CVB1 vaccine was developed and tested for its immunogenicity and safety in BALB/c and NOD mice. Prediabetic NOD mice were vaccinated, infected with CVB1 or mock-treated to compare the effect on diabetes development.

Results

Vaccinated mice produced high titres of CVB1-neutralising antibodies without signs of vaccine-related side effects. Vaccinated mice challenged with CVB1 had significantly reduced levels of replicating virus in their blood and the pancreas. Prediabetic NOD mice demonstrated an accelerated onset of diabetes upon CVB1 infection whereas no accelerated disease manifestation or increased production of insulin autoantibodies was observed in vaccinated mice.

Conclusions/interpretation

We conclude that the prototype vaccine is safe and confers protection from infection without accelerating diabetes development in mice. These results encourage the development of a multivalent enterovirus vaccine for human use, which could be used to determine whether enterovirus infections trigger beta cell autoimmunity and type 1 diabetes in humans.
Appendix
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Metadata
Title
A preclinical study on the efficacy and safety of a new vaccine against Coxsackievirus B1 reveals no risk for accelerated diabetes development in mouse models
Authors
Pär G. Larsson
Tadepally Lakshmikanth
Olli H. Laitinen
Renata Utorova
Stella Jacobson
Maarit Oikarinen
Erna Domsgen
Minni R. L. Koivunen
Pascal Chaux
Nicolas Devard
Valerie Lecouturier
Jeffrey Almond
Mikael Knip
Heikki Hyöty
Malin Flodström-Tullberg
Publication date
01-02-2015
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 2/2015
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-014-3436-0

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