Vaccines for Type 1 Diabetes, An Update
Scientists have been working to develop an immunotherapy--a vaccine--that targets the cause of type 1 diabetes to prevent or at least delay onset of the disease. Although it's too early to break out the champagne, advances in the quest for vaccines for type 1 diabetes are being made. Here's a brief update.
How can a vaccine help type 1 diabetes?
Type 1 diabetes is an autoimmune disease, which means the body destroys a healthy part of itself; in the case of type 1 diabetes, what is destroyed are the beta cells, which produce and secrete insulin in the pancreas. Why this occurs is still a mystery, although there are some theories.
Many years of research has revealed that a key cause of type 1 diabetes is that the autoimmune T lymphocytes (T cells) destroy the beta cells in the pancreas, and that the cytokine tumor necrosis factor (TNF) has potential as an immunotherapy to tackle this problem. Why?
Because in lab and animal studies, TNF destroys the "bad" T cells but not healthy ones. Tumor necrosis factor also may improve production of "good" regulatory T cells (Tregs), which are believed to suppress the bad T cells.
With this research in mind, Harvard researcher Denise Faustman, MD, PhD, and colleagues conducted a small, proof-of-concept study using the Bacillus Calmette-Guerin (BCG) vaccine in six individuals (mean age, 35 years) with long-standing type 1 diabetes. Such a study is done to establish that an idea or process is feasible.
The BCG vaccine was chosen because it stimulates innate immunity by prompting the production of TNF. The six patients were given either injections of BCG or a placebo. Others in the study included 6 healthy controls who were paired with the selected type 1 diabetes patients, as well as 73 reference patients with type 1 diabetes or healthy controls.
The vaccine and placebo injections were given on two occasions, four weeks apart. Blood samples were then collected and analyzed throughout the study up to week 20.
The researchers discovered that patients who received the BCG vaccine:
- Showed an increase in dead "bad" T cells (insulin-autoreactive T cells)
- Had an improvement in insulin sensitivity as demonstrated by transient but significant increases in C-peptide levels in two of the three vaccine recipients. C peptide levels are important because it is linked with insulin when they are produced in the pancreas. The level of C-peptide in the blood reveals how much insulin the pancreas is making.
- Showed increases in the number of Tregs compared with paired healthy controls
For now, the researchers concluded that the BCG vaccine, when given at low doses, seems to be safe and well tolerated. They noted that their work "paves the way for either higher doses or more frequent BCG administered in future trials for patients with advanced disease to maintain or restore C-peptide levels."
Other immunotherapy research for type 1 diabetes
The BCG vaccine is not the only research being done in the area of immunotherapy for type 1 diabetes. Here's a brief rundown of a few other efforts.
- Teplizumab is an immunotherapy currently in a Phase II clinical trial. The trial is attempting to determine if therapy can help to prevent or delay the onset of type 1 diabetes in people identified as being at very high risk for the disease by intervening in the immune process that causes the destruction of beta cells during the early stages of the disease. Previous studies of teplizumab have shown that the immunotherapy can reduce the loss of insulin production during the first year after diagnosis of type 1 diabetes.
- On May 28, 2012, the Food and Drug Administration (FDA) granted Orphan Drug designation for DiaPep77® for the treatment of patients with type 1 diabetes who still have residual beta cell function. DiaPep77 works by modulating the immune system to prevent the destruction of beta cells and preserve their function. The vaccine is currently in Phase III clinical trials in more than 120 medical centers.
- Abatacept, a drug approved for rheumatoid arthritis, is being studied as immunotherapy for type 1 diabetes. In a double-blind, randomized trial, 112 patients with recent onset type 1 diabetes received abatacept or placebo as 27 infusions over 2 years. Compared with placebo, abatacept increased C-peptide by 59% and delayed reduction of C-peptide as well.
These and other attempts to discover vaccines for type 1 diabetes are ongoing. Individuals who are interested in learning more about clinical trials involving immunotherapy for type 1 diabetes should talk to their healthcare provider or visit the clinical trials website.
Faustman DL et al. Proof-of-concept, randomized, controlled clinical trial of Bacillus-Calmette-Guerin for treatment of long-term type 1 diabetes. PLoS One 2012 7(8): e41756
Orban T et al. Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomized, double-blind, placebo-controlled trial. 201 Lancet 378 (9789): 412-19
Pozzilli P, Strollo R. Immunotherapy for type 1 diabetes: getting beyond a negative first impression. Immunotherapy 2012 Jul; 4(7): 655-58