A Reverse Vaccine and Type 1 Diabetes

Results of a proof-of-concept study have shown that treatment with a so-called reverse vaccine in patients with type 1 diabetes mellitus can preserve pancreatic function, among other benefits.

We all know what vaccines do; they induce a specific response from our immune systems, safely teaching them how to respond to a future threat.

A reverse vaccine is based on this concept, except instead of inducing a response, it inhibits or turns off a specific response.

Working on the premise that immunity to insulin is one of the fundamental aspects underlying the pathophysiology of type 1 diabetes, researchers are reporting online in the journal Science Translational Medicine about just such a vaccine: BHT-3021.

BHT-3021

BHT-3021 is an engineered DNA plasmid. It encodes a modified form of pro-insulin. Results of this proof-of-concept study show that it increases c-peptide levels in patients with type 1 diabetes mellitus.

It also decreases bloodstream levels of certain cytotoxic CD8 T-cells found in patients' islet cells. It accomplished this without causing any other major problems.

And that's a big deal, since it's a risky proposition to try to limit anyone's antigenic response because you can try and be as specific as you like, but you don't know if you're also blocking other functions of the immune system.

For the sake of specificity, the researchers wrote:

The vaccine is engineered to reduce the immunogenicity of the encoded pro-insulin by substituting CpG hexameric motifs, which stimulate the innate immune response, with GpG hexameric nucleotide sequences, known to modulate innate immunity.

The Study

The study involved 80 adult patients, median age 30, who had type 1 diabetes for less than five years. They received an intramuscular injection of the reserve vaccine for three months and were compared with a placebo arm.

Specifically, patients in the treatment arm saw an increase of 19.5 percent in levels of C-peptide, compared to a decrease of 8.8 percent in the placebo arm.

What's Next

The vaccine has actually reversed type 1 diabetes in mice. However, in humans it appears the clinical relevance is limited to being beneficial only to people who have not yet been diagnosed.

As a concept, the reverse vaccine's ability to actively block the autoimmune response in patients with type 1 is intriguing. As a practical or viable option, it remains far off on the distant horizon.

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