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Salmonella-based oral vaccine for T1 diabetes successful in animal model.

Type 1 diabetes is an autoimmune disease, meaning that the underlying problem is with the immune system.  It is still unclear as to why the body’s immune system attacks and destroys the part of the pancreas that produces insulin,  resulting in a loss of metabolic control and high blood sugar levels.  Earlier studies have investigated inhibiting all immunity in type 1 diabetes and have shown good short-term results, however, they also show serious side-effects.  Now, a study from researchers at the Beckman Research Institute of City of Hope shows that a vaccine using live Salmonella is a safe and effective way to prevent diabetes in mice.  The team state that their vaccine is a very safe and effective targeted immunotherapy which they believe is a great place to start in the development of a vaccine to stop type 1 diabetes.  The results were presented at ENDO 2016.

Previous studies show that the current standard of care for type 1 diabetes is to treat the symptom, namely high blood sugar levels, without addressing the underlying autoimmunity.  One of the most promising approaches to restore the balance within the immune system is the oral administration of diabetic autoantigens, which diminishes the islet-specific destructive responses and induces regulatory responses. Evidence suggests that presentation of antigen by the gut associated lymphoid tissue would improve tolerance induction, which would be augmented in the presence of specific tolerogenic cytokines such as TGFβ and IL10.  Recent studies have hinted that immunotherapies given in the right way with the right dose and probably as a combination therapy could be effective to treat people with diabetes.  The current study develops an oral vaccine for type 1 diabetes based on live-attenuated Salmonella.

The current study utilised Salmonella typhimurium bacteria in combination with other small regulatory proteins called cytokines and a low dose of an immunosuppressive drug called Anti-CD3. Results show that the vaccine re-balances the immune system and prevents the attack on the insulin-producing cells.  Data findings show that the vaccine prevented diabetes in non-obese diabetic mice and restored normal glucose tolerance.

Results show that the combination therapy of oral vaccination with mPPI, TGFβ and IL10 combined with sub-therapeutic dose of anti-CD3 prevented diabetes in non-obese diabetic mice and restored normal glucose tolerance. Data findings show that the combined vaccine therapy increases regulatory T cells in splenocytes, and local regulatory T cells in the pancreas of vaccinated non-obese diabetic mice. The lab note that the combination therapy also significantly increased the regulatory cytokines IL10 and IL2, and inhibited inflammatory Interferon gamma, whose aberrant expression is associated with a number of autoimmune diseases.

The team surmise that their findings indicate that the vaccine suppressed the autoimmunity and increased regulatory mechanisms leading to a conclusion that a Salmonella-based oral vaccine is a promising therapy for the prevention of type 1 diabetes.  For the future, the researchers now plan human studies.

Source: Beckman Research Institute of City of Hope

Under a very high magnification of 12000X, this colorized scanning electron micrograph shows a large grouping of Gram-negative Salmonella bacteria. REUTERS/Janice Haney Carr/CDC/Handout
Under a very high magnification of 12000X, this colorized scanning electron micrograph shows a large grouping of Gram-negative Salmonella bacteria. REUTERS/Janice Haney Carr/CDC/Handout

 

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