Lawrence Steinman’s ‘Reverse Vaccine’ Targets Immune Response in Type 1 Diabetes


Sometimes, when you’re stuck and spinning your wheels without making much forward progress, putting it in reverse can get you going. That’s what Dr. Lawrence Steinman and his colleagues are doing by attempting to cure type 1 diabetes with a unique and groundbreaking “reverse vaccine.”

“This, right now is very promising,” Steinman says following a clinical trial where 80 people were treated for 12 weeks then followed for an additional year with his  “reverse vaccine” procedure. “We not only saw better production from [insulin producing] beta cells, but we also saw significant improvement regarding managing the immune response so that the beta cells remained active and alive.”

Steinman’s treatment is two-step process. The first step involves using a plasmid, which is a circular strand of artificial DNA, as a drug to encode “pro-insulin,” which is a nonfunctioning precursor to insulin. The plasmid makes its way into muscle cells, which in turn begin to produce pro-insulin. Unlike beta cells, however, muscle cells are unable to convert pro-insulin into functional insulin peptides.

This action is similar to many other attempts to cure type 1 diabetes that replace insulin-producing beta cells. Many of these attempts have stalled, however, not because the beta cells are faulty, but because the body’s immune system aggressively attacks and eliminates the newly introduced cells producing the insulin.

So why bother making non-functional insulin? This is what makes the drug truly exciting.

When the muscle cells begin producing pro-insulin, the cells of the immune system are tricked into thinking pro-insulin is a normal protein, not a foreign invader. This process, called “tolerization,” ideally results in immune cells learning that insulin is a good, “self” protein, even when encountered around beta cells. Thus, the DNA plasmid encoding pro-insulin in muscle cells helps to shut off the body’s specific immune response and the invasion of the new beta cells. The body’s immune system is thwarted in its attack of the beta cells, and beta cells are left intact and healthy to produce insulin.

Dr. Lawrence SteinmanThis method differs sharply from using immunosuppressant drugs to combat the body’s immune response to what it sees as an invader that may cause harm. In islet cell transplantation, for instance, insulin-producing islet cells from a cadaver are transplanted into a type 1 diabetic’s liver to make insulin in much the same way the islet cells in the pancreas once did. Rather than having the specific immune response shut off so that the islet cells may survive, recipients of such transplants take broad range immunosuppressants to keep the body’s immune system from attacking the new cells, much like recipients of full-blown organ transplants.

This rigorous immunosuppression regime for islet cell transplant subjects, however, has been found to actually harm the very delicate islet cells. Instead of using this shotgun approach that suppresses wide swaths of the immune system, the “reverse vaccine” takes a rifle shot to suppress only the specific immune response that affects the beta cells.

“It’s similar to allergies,” Steinman says. “There are millions of people who go to the allergist and they are tested to see what their specific allergy is so they can be treated appropriately. You don’t, for instance, want to take broad-based cyclosporine [an immunosuppressant] for a peanut allergy.”

The “reverse” in the “reverse vaccine” means that the DNA plasmid drug is shutting off a targeted immune response to keep cells alive. Other vaccines, such as the flu vaccine, seek to boost the immune response to, in this case, influenza, thereby eliminating it.

Whether the “reverse vaccine” will ultimately result in a cure is unknown at this time, Steinman says. But, results from the clinical trial already indicate benefits for helping type 1 diabetics better control their condition.

Because insulin levels are notoriously difficult to accurately measure and track in blood, the trial for the “reverse vaccine” instead tracked subjects’ C-peptide levels. C-peptides are an indicator of insulin production, and, according to some studies, may play a role in mitigating diabetic complications, such as blindness and kidney disease.

Commenting on the study in the June 2013 issue of Inside Stanford Medicine, Richard Insel, MD, chief scientific officer of the JDRF—also known as the Juvenile Diabetes Research Foundation—said, “Individuals with preserved C-peptide are at lower risk of long-term eye, kidney and nerve complications. So it’s intriguing that in this [Steinman’s] study, C-peptide levels were preserved or, at times, increased while patients were receiving the vaccine.”

Even minimal maintenance of insulin production, indicated by C-peptide levels, could be very beneficial over the long term in preventing the complications of type 1 diabetes. “To be realistic, someone’s going to cure type 1 diabetes,” Steinman says. “But, in the meantime, if we can reduce complications then we’re doing some good.”

Steinman adds that so far the safety signals from the trial are good, meaning there are no serious side effects.

The next step in the process, he says, is to conduct a more expansive clinical trial on more subjects over a longer period of time– an effort for which he and other researchers are seeking funding.

Meanwhile, Dr. Lawrence Steinman and his colleagues are not the only ones working on perfecting a “reverse vaccine.”

“It’s a global effort,” he says. “There is very good work going on around the world in this area, and we’re getting closer.”

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8 years ago

I’m absolutely interested in volunteering to be a part of this trial, some information on who to contact would be great!

8 years ago


8 years ago

I wonder how I can become one of the people they use to test this… I would totally do it!

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