Developing a vaccine for Type 1 diabetes through targeting enteroviral infections

Abstract

Type 1 diabetes (T1D) is a chronic disease caused by the destruction of insulin producing β-cells in the pancreas. Studies carried out during the past decades have implied that enteroviruses could be an important causative agent. These findings have generated efforts aiming at developing vaccines against these viruses and testing their efficacy against T1D in clinical trials. Extensive work has been carried out to define the serotype of enteroviruses which are linked to T1D and which should be included in the vaccine, and experimental vaccines have been shown to be effective and safe in mouse models. Large-scale studies are currently in progress to increase the confidence in the scientific concept of the enterovirus-diabetes association, paralleling the efforts aimed at starting the clinical development of the vaccine. This review summarizes recent progress in this field and the scenarios regarding this development process.

Keywords::

• antiviral drugs
• enterovirus
• Type 1 diabetes
• vaccine

Acknowledgements

The authors would like to thank H Honkanen, S Oikarinen, M Oikarinen, A Kondrashova, A BabakSioofy-Khojine, J Laiho, O Laitinen, M Flodström-Tullberg, the Steering Committee of the Finnish Diabetes Prediction and Prevention (DIPP) study and all other collaborators contributing to the findings and discussions summarized in this review.

Financial & competing interests disclosure

H Hyöty and M Knip are minor (<5%) shareholders and members of the board of Vactech Ltd., which develops vaccines against picornaviruses. This work was supported by the Competitive Research Funding of the Tampere University Hospital, the Juvenile Diabetes Research Foundation (JDRF), the Academy of Finland, Sohlberg’s Foundation, Sigrid Juselius Foundation and the European Commission (VirDiab, EPIVIR, PEVNET and DiabImmune projects of the FP-7 Programme). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Type 1 diabetes (T1D) is a severe disease, the incidence of which is increasing worldwide.

• Virus infections cause diabetes in animals.

• One virus group, EVs, has been associated with human T1D in numerous studies.

• EVs have a natural tropism to the pancreas and they infect insulin-producing cells, which are destroyed in T1D.

• Recent evidence suggests that the majority of patients with T1D have a low-grade enterovirus infection in their pancreas.

• The association between EVs and T1D has been linked to certain specific enterovirus serotypes.

• Experimental vaccines have been produced against these enterovirus types and shown to be effective and safe in mice.

• Both scientific and socioeconomic reasons argue for the need of clinical trials testing the efficacy of such vaccines in the prevention of T1D.

Notes

EV: Enterovirus; T1D: Type 1 diabetes.