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Vaccine Blocks Suspected Type 1 Diabetes Infections


(frolicsomepl, Pixabay)

7 May 2020. A candidate vaccine is shown in lab animals to produce a strong immune response against a virus causing a range of diseases, and possibly blocking type 1 diabetes. Results of the study by a team from Karolinska Institutet in Stockholm, Sweden and Tampere University in Finland appear in yesterday’s issue of the journal Science Advances.

The team led by Karolinska infectious disease researcher Malin Flodström-Tullberg and Tampere computational protein chemist Vesa Hytönen are investigating Coxsackie B viruses. These common viruses are known to cause infections that usually result in no or mild symptoms similar to a cold, but can also cause more serious disorders including myocarditis or infections in heart tissue and aseptic meningitis, inflammation in the brain and spinal cord.

The Coxsackie B virus is also a suspected trigger of type 1 diabetes and other autoimmune disorders. Type 1 diabetes is an autoimmune disorder where islet cells in the pancreas do not produce insulin. The disease is diagnosed primarily in children or young adults, where the immune system is tricked into attacking healthy cells and tissue as if they were foreign invaders, in this case, insulin-producing islet cells. Five to 10 percent of people diabetes have the type 1 form.

The Karolinska-Tampere team designed their vaccine to cover all six known Coxsackie B sub-types, using inactivated viruses aimed at each sub-type.  The researchers first tested the vaccine in lab mice, looking mainly for signs of adverse effects. The mice received an initial vaccine dose followed by an added dose at 14, then at 28 days following the first injection, then were monitored for another 56 days. The team performed similar tests with non-obese mice induced with diabetes.

The results with both sets of mice show no signs of adverse effects, but the mice also generated strong, neutralizing antibodies against all six Coxsackie B sub-types. Further tests tested the vaccinated mice exposed to two sub-types of the Coxsackie B virus. The results show the vaccinated mice produced a strong immune response with neutralizing antibodies, with no replicating viruses in their blood after three days. Unprotected mice, however, after three days developed signs of pancreatitis, a disease sometimes caused by Coxsackie B.

Another round with mice tested the vaccine against the Coxsackie B sub-type associated with myocarditis, inflammation of heart tissue. Mice receiving the vaccine produced neutralizing antibodies and blood samples show no viruses in their blood after five days. Among unprotected mice, however, Coxsackie B viruses were found in the hearts and pancreas, with one mouse dying before five days.

One more test with mice assessed the Coxsackie B vaccine as a preventive measure against type 1 diabetes. The mice in this case were genetically engineered to be susceptible to infections in beta cells produced by the pancreas. The animals were given either the vaccine or a carrier chemical, and exposed to two Coxsackie B sub-types associated with type 1 diabetes. Unvaccinated mice developed hyperglycemia, or high glucose levels in their blood and experienced damaged pancreas tissue, while the vaccinated mice remained with normal blood glucose levels and showed no damaged pancreas tissue.

The researchers then tested the vaccine with rhesus macaques, a monkey species, closer in similarity to humans. The monkeys received two doses of the vaccine, the second after 28 days, with the team also testing the vaccine with and without an adjuvant or booster. The tests reconfirmed the vaccine’s safety with the monkeys showing no adverse effects in weight, body temperature, glucose levels, or changes in liver enzymes. Results also show high production of neutralizing antibodies against Coxsackie B, in both the vaccine alone and with adjuvant, suggesting no adjuvant is needed.

While a definite causal link has not been made between Coxsackie B viruses and type 1 diabetes, the researchers say this study adds more evidence supporting that connection. Heikki Hyöty, one of the co-authors from Tampere University, is a founder of the company Vactech Oy in Tampere, licensing the technology for a preventive vaccine against type 1 diabetes. In March, the company received a U.S. patent for its type 1 diabetes vaccine protecting against Coxsackie B viruses. Vactech Oy is collaborating with Provention Bio in Oldwick, New Jersey on the vaccine. Senior author Malin Flodström-Tullberg is an adviser to Provention Bio.

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