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A vaccine that could prevent Type 1 Diabetes
“The aim was to develop a vaccine that could prevent a significant number of Type 1 Diabetes cases. Additionally, the vaccine would protect from infections caused by enteroviruses such as the common cold, myocarditis, meningitis and ear infections. However, in light of current research, the vaccine could not be used to cure pre-existing diabetes.”
Type 1 Diabetes is caused by the destruction of insulin-producing cells in the pancreas, and is treated with daily insulin injections. Type 1 Diabetes is becoming more common and cases of it occur in Finland more than anywhere else in the world. It places a significant burden on public health care and can reduce the quality of life and the average life expectancy. It has been estimated that a patient with Type 1 Diabetes will cause society expenses worth 1 million EUROs on average during their lifetime.
The connection between viral infections and Type 1 Diabetes has been researched for over 25 years at the Faculty of Medicine and Life Sciences at the University of Tampere. Their results indicate that one virus group, enteroviruses, play a part in developing Type 1 Diabetes which can infect the insulin-producing cells of the pancreas damaging them permanently.
The research phase beginning now is the result of a long period of negotiations between several stakeholders. It will be funded by the US-based company Provention Bio. Other partners include The Juvenile Diabetes Research Foundation, the largest foundation funding research on Type 1 Diabetes in the world, and Vactech Oy a Finnish company that has developed the necessary vaccine technology. Professor Heikki Hyöty (University of Tampere) and Professor Mikael Knip (University of Helsinki) are co-founders in Vactech Oy.
Type 1 diabetes is caused by an immune-mediated process that damages insulin-producing beta cells in the pancreatic islets. The subclinical phase of the disease can be identified by detecting autoantibodies against islet antigens, including islet cell antibodies (ICAs), insulin antibodies (IAAs), insulinoma-associated protein 2 antibodies (IA-2As), zinc transporter 8 antibodies and GAD antibodies .
Enteroviruses have been linked to type 1 diabetes in studies showing an increased frequency of these viruses in the blood and pancreas of diabetic and autoantibody-positive individuals [2, 3, 4] and in serological studies showing an increased frequency of enterovirus antibodies in diabetic and autoantibody-positive participants [5, 6, 7, 8, 9, 10, 11]. However, this association has not been seen in all studies .
Relatively few prospective studies have been carried out even though such studies would be optimal for evaluating the possible role of enterovirus infections in the most important phase of pathogenesis, the initiation of islet autoimmunity. The results from such studies have suggested that enterovirus infections, diagnosed by serology or by direct detection of the virus from blood, are associated with the appearance of islet autoantibodies long before clinical diabetes is diagnosed [6, 9, 11, 12]. In contrast, the detection of the virus in stools has not shown such an association [13, 14], and in one study in which both blood and rectal swabs were analysed, no association at all was found . However, these negative findings have been based on small cohorts and infrequent sample collection. In addition, the Diabetes and Autoimmunity Study in the Young (DAISY) study in the USA has evaluated the possible role of enterovirus infection in the progression of islet autoimmunity to clinical disease and reported more enterovirus infections detected by the presence of virus in blood but not in stools in children who progressed to diabetes .
The current study is the largest to date in which enteroviruses have been analysed in longitudinal stool samples collected from children who developed signs of a beta cell-damaging process during their prospective observation. Since this study was based on a prospective birth cohort, we were able to analyse time-dependent associations between enterovirus infections and the initiation of the beta cell-damaging process.
Keywords: TERRA, R-loop, RNA-DNA hybrid, RNase H2, telomere, DDR, senescence, Rat1, Rif2
Finnish research played a key role along with the Type 1 Diabetes Prediction and Prevention study (DIPP) which has significantly advanced research on a connection between viruses and diabetes. Additionally, collaboration with Vesa Hytönen PhD, Assistant Professor and other Tampere-based professionals, has been crucial in developing vaccines. Other noteworthy partners include the Karolinska Institutet in Stockholm, several universities and research institutes in Finland and abroad as well as Vactech Oy. Research has been funded by several different groups, such as the Academy of Finland, TEKES, the Sigrid Juselius Foundation, the Reino Lahtikari Foundation, the Diabetes Research Foundation, the European Union and the Juvenile Diabetes Research Foundation (JDRF).
The Massachusetts General Hospital Immunobiology Laboratory conducts basic and translational research focused on discovering novel treatments for autoimmune diseases, with a specific focus on type 1 diabetes.
The Massachusetts General Hospital Immunobiology Laboratory
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Enterovirus in pancreatic tissue, stained brown.
Image Credit: Heikki Hyöty PhD, Tampere University, Helsinki, Finland