Possible vaccine for virus linked to type 1 diabetes

While some 50,000 Finns have type 1 diabetes (sometimes known as juvenile diabetes) the causes of the disease remain unknown. There is a genetic component, but also environmental factors are needed for the disease to develop. One such factor believed to be significant in type 1 diabetes is infections caused by an extremely common group of enteroviruses. This sub-group in question is the Coxsackie B (CVB) comprising six strains that can cause the common cold. However, CVBs can also cause more serious infections leading to, for example, myocarditis and meningitis.

According to many scientific observations, one hypothesis suggests that CVB play a part in the development of type 1 diabetes. The disease is characterised by an autoimmune attack on the insulin-producing beta cells of the pancreas, and it is possible that the virus infection somehow initiates this attack by the immune system.

Epidemiological studies, in which children with a genetic risk profile for type 1 diabetes were monitored by blood tests over a period of many years, indicate that CVB could be a pathogenic contributor. There are also autopsy findings suggesting that CVB might be involved in the development of type 1 diabetes. However, this remains hypothetical as the connection is yet to be proven, albeit it is a hypothesis that is well-established amongst diabetes researchers.

Researchers at Tampere University, Karolinska Institutet in Sweden and University of Jyväskylä have now produced a vaccine that protects against all six known strains of CVB. The vaccine was tested in different animal models and was shown to protect mice infected with CVB from developing virus-induced type 1 diabetes.

The researchers then tested the vaccine in rhesus monkeys that have very similar genetics to humans. In these animals, the vaccine worked well and induced antibodies to CVB suggesting it could protect against the virus.

“The results give important scientific support to an ongoing clinical development program aiming at testing a similar clinical vaccine in humans,” says Professor Heikki Hyöty from Tampere University who participates in the clinical development program. The program is carried out by an American pharmaceutical company in collaboration with a Finnish biotech company.

Assuming the vaccine is safe in the initial trails, the plan is to give the vaccine to children with a genetic risk profile for type 1 diabetes. The researchers write that if the number of children that develop type 1 diabetes decreases after vaccination or if none develop the disease it will confirm that CVB are a triggering environmental factor.

“Our hope is that the vaccine will prove effective against CVB infections and that it will then be possible to administer it to children,” says Malin Flodström-Tullberg, professor of type 1 diabetes at the Department of Medicine, Karolinska Institutet, Huddinge, and the study’s corresponding author.

“It would be fantastic if the cases of type 1 diabetes that we currently suspect to be caused by the Coxsackievirus could be prevented, although the exact number is difficult to estimate. At the same time, the vaccine would give protection against myocarditis, which can have a more severe course in both children and adults, and against many kinds of cold, which keep many people away from school and work.”

“This work was the result of close Tampere-Stockholm teamwork. The results are exiting and support the ongoing development of the clinical vaccine towards human trials” says Vesa Hytönen, associate professor in cell and molecular biology at the Faculty of Medicine and Health Technology, Tampere University.

The study was financed with grants from Business Finland, the Academy of Finland, the Childrens’ Diabetes Fund and the Strategic Research Programme in Diabetes at Karolinska Institutet. The US pharmaceutical company conducting the tests is Provention Bio, for which Malin Flodström Tullberg is scientific advisor. Provention collaborates with the Finnish company Vactech Oy, which owns patents in this field, and of which Heikki Hyöty, professor at Tampere University and co-author of the study, is one of the founders.

A hexavalent Coxsackievirus B vaccine is highly immunogenic and has a strong protective capacity in mice and non-human primates, V. M. Stone, M. M. Hankaniemi, O. H. Laitinen, A. B. Sioofy-Khojine, A. Lin, I. Diaz Lozano, M. A. Mazur, V. Marjomäki, K. Loré, H. Hyöty, V. P. Hytönen, M. Flodström-Tullberg, Science Advances, 6 May 2020