An experimental vaccine reduced signs of multiple sclerosis in mice by preventing their immune systems from targeting their own cells. If it works in humans, the vaccine could potentially treat multiple sclerosis and others autoimmune diseases, including type 1 diabetes and coeliac disease.
Autoimmune conditions occur when a person’s immune system mistakenly attacks their own cells. With multiple sclerosis, for example, immune cells damage the protective coating around nerves, leading to issues such as muscle spasms, brain fog and blurred vision.
at the University of Chicago and his colleagues developed a vaccine to halt this faulty immune response. Whereas traditional vaccines train the immune system to identify and counteract specific molecules, their “inverse vaccine” does the opposite, unwinding a learned immune response.
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It works by hijacking a system for clearing dead cells, he says. When our cells die, they develop a specific molecular pattern on their surface, like an out-of-service sign. That way, once they reach the liver, the organ recognises them as waste and removes them. The liver also signals to the immune system that these dead cells are not a threat, and therefore immune cells shouldn’t mount an attack on them. This inhibits any unwanted responses.
Hubbell and his team modified molecules that spur immune reactions, called antigens, by adding a structure to them that mimics this out-of-service sign. Once in the body, the liver treats this structure like a dying cell, clearing it away and informing the immune system that it, along with the accompanying antigen, is not a threat. This teaches the immune system to ignore the antigen in the future, thus undoing an immune response, says Hubbell.
To see if the vaccine could treat autoimmunity, the researchers used it on 10 mice with signs of multiple sclerosis. These animals had previously received an injection of a single antigen that caused their immune systems to attack the protective coating of nerves, much like multiple sclerosis does. The vaccine targeted this particular molecule.
The researchers tracked symptoms in the animals using a scale of 0 to 5, with higher scores indicating greater impairments. Two weeks after the mice received the vaccine, they scored, on average, less than 1. Meanwhile, an equal number of rodents given saltwater injections scored higher than 2.5, indicating the vaccine dampened autoimmune responses. Hubbell and his team found the vaccine was effective in non-human primates as well.
The effect in mice was comparable to an immune-suppressing medication commonly used in autoimmune conditions. Unlike this medication, though, the vaccine doesn’t need to be taken daily and doesn’t increase the risk of infections. “It would be great to not have to suppress someone’s immune system chronically, but rather vaccinate so that you could have a more curative approach,” says Hubbell.
A slightly different version of the reverse vaccine is currently in a phase 1 clinical trial for multiple sclerosis, he says. But it remains to be seen whether it can halt the condition’s progression.
“The trouble is multiple sclerosis is not caused by one antigen,” says at Yale University. “Each patient is different, and we’re finding autoreactivity to a number of different antigens. We can’t test them all.” As such, Hafler doesn’t believe these findings will translate to humans.
Hubbell says the vaccine can also be tweaked to target different antigens, meaning it could treat an array of autoimmune conditions. For instance, a similar injection showed promise in a small trial of people with coeliac disease.
Nature Biomedical Engineering
