‘Inverse vaccines’ could turn autoimmune treatment upside down

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The writer is a science commentator

Vaccines teach the immune system to remember, by laying down molecular memories of viruses and bacteria. Infection reawakens memories of these pathogens, stimulating the immune system to bite back at a known foe.

But over the past decade or so scientists have been exploring “inverse vaccines”, which instead encourage the immune system to forget — with the specific aim of treating autoimmune diseases such as multiple sclerosis (MS) and type 1 diabetes. These conditions can be thought of as friendly fire, with the immune system wrongly identifying the body’s own healthy tissue as hostile and targeting it for destruction.

Now researchers in Illinois have developed an inverse vaccine that appears to reverse the progression of an MS-like disease in mice, by using the liver to reset immunity. The finding opens up fresh avenues for treating autoimmune disorders and is another shot in the arm for immunotherapy, an approach that harnesses a patient’s own immune system to combat disease.

Of course, our biological defences do not go haywire at every foreign interloper. The liver, for example, processes what we eat so that the proteins filtering through do not constantly put our immunological haunches up.

Jeffrey Hubbell of the University of Chicago’s Pritzker School of Molecular Engineering led a team to see if the liver could similarly induce a tolerance to the antigens, usually cellular proteins, that trigger autoimmune diseases.

MS results in the immune system mistakenly attacking myelin, the protective sheath surrounding nerves and the spinal cord; symptoms include dizziness, spasms and difficulty walking. The disease, which can alternately flare up and subside, can be modelled in mice. By despatching myelin antigens to the liver — attached to a sugar that acts as a kind of luggage label — the researchers were able to dial down the immune response in affected mice. Their results were published this month in the journal Nature Biomedical Engineering.

Interestingly, Hubbell explains, when the vaccine was given to mice recovering after a flare-up, the animals did not relapse. “That’s the part of the paper that gave me the most joy,” he tells me, suggesting a vaccine could be used to treat illness as well as prevent it, potentially offering relief to current sufferers. The researchers previously showed the same technique could stop the onset of type 1 diabetes in mice.

Hubbell co-founded a company, Anokion, to take these ideas into the clinic. It is conducting early-stage human clinical trials on liver-targeted vaccines for coeliac disease and MS, and exploring a vaccine candidate for type 1 diabetes.

Treatments for autoimmune diseases often comprise life-long immunosuppressants, but these can leave patients vulnerable to opportunistic infections and cancer. With autoimmune disorders affecting up to 10 per cent of the global population, a large, eager patient pool awaits those able to crack a more tailored approach. Anokion is in distinguished company: BioNTech is also exploring an mRNA vaccine for MS, publishing encouraging preliminary results in 2021.

The noted cardiologist Eric Topol, director of the Scripps Research Translational Institute in California, hailed Hubbell’s team’s work in his newsletter but cautioned that the journey to a working vaccine would be a “huge challenge”, given that MS in humans is not well understood. Hubbell says he is optimistic but “not so cavalier to say we’ve solved it. We stand a chance.”

Given the immense complexities of autoimmune diseases, a long slog is more likely than a miracle fix. Still, that would befit immunotherapy’s slow beginnings. William Coley, born in 1862, was an American bone surgeon who, distressed at a teenage patient dying from bone cancer, vowed to find better treatments. Raking through medical archives, he discovered the notes of a patient whose tumour shrank after contracting a bacterial infection — as well as other reports of spontaneous remission — and suspected the bacteria was triggering a beneficial change in immunity. He went on to inoculate cancer patients with live bacteria, saving some but killing others.

Ultimately, Coley lost the argument to rivals championing radiation therapy, but his contribution to immunotherapy has since been recognised. Today, when Hubbell expresses gratitude for the scientists who paved the way for a “whole new time, a new era in translational immunology”, it is hard not to think of the bone surgeon who once gazed helplessly at a teenager on her deathbed.  

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