Elledge zeroes in on measles

Posted

Measles causes long-term damage to the immune system, leaving children who have had it vulnerable to other infections long after the initial illness has passed, research has revealed, led by Paris native and Paris High School graduate Stephen Elledge.

The disease itself can cause a severe and sometimes deadly illness, but two new studies published Thursday, Oct. 31, found that even when patients recover, the virus can inflict lasting harm on their immune systems.

“We’ve found really strong evidence the measles virus is actually destroying the immune system,” said Elledge, senior author of one of the two papers published this week. “The threat measles poses to people is much greater than we previously imagined.”

Globally, measles affects more than seven million people each year and causes more than 100,000 deaths. Reduced vaccination rates have led to a nearly 300 percent increase in measles infections since 2018.

Scientists call the effect immune amnesia. During childhood, as colds, flu, stomach bugs and other illnesses come and go, the immune system forms something akin to a memory that it uses to attack those germs if they try to invade again.

The measles virus erases that memory, leaving the patient prone to catching the diseases all over again.

To profile each person’s past exposures to infectious disease, the authors of the Harvard study used VirScan, a tool that can detect antibodies to hundreds of viruses and many types of bacteria. The tool was developed by Elledge, a geneticist at the Harvard Medical School and Brigham and Women’s Hospital.

Comparing the before-and-after samples, the test found that measles wiped out 11 percent to 73 percent of a child’s antibodies against an array of viruses and bacteria. Elledge called the depletions shocking — and said that the biggest drops tended to occur in children with the severest cases of measles.

The findings make the need for measles vaccination even more urgent, because it protects children against much more than measles, the researchers said.

Two studies of unvaccinated children in an Orthodox Protestant community in the Netherlands found that measles wipes out the immune system’s memory of previous illnesses, returning it to a more baby-like state — and also leaves the body less equipped to fight off new infections.

Measles eliminated between 11 percent and 73 percent of children’s protective antibodies, the research found.

Measles is highly contagious and can be spread when someone with the virus coughs, sneezes or exhales. Once inside the respiratory tract, the virus penetrates immune cells that sit at the interface between the lungs and bloodstream. From there, the virus replicates and spreads to immune cells throughout the body.Elledge’s team looked at antibodies in the blood — the proteins produced by immune cells — and found that 11-73 percent of the antibody memory bank had been erased after measles.

The research found the MMR vaccine itself did not produce immune suppression, meaning that recipients get the benefit of lifelong immunity to measles infection without the damaging effects of natural infection.

People who contract measles aren't out of the woods after their rash fades and their fever subsides.

They're then more vulnerable to other bacterial and viral infections — even those they've already been vaccinated against or have had before.

That's because measles virus attacks the cells that serve as the immune system's memory, wiping out established resistance to disease, a pair of new studies report.

As much as three-quarters of a person's immune memory can be wiped out by the amnesia caused by the measles virus, one team of researchers reported in the November issue of the journal Science.

"The measles virus is resetting your immune clock to a naive state, and all of the protection you got by living through other viral and bacterial infections is reduced going forward," said senior researcher Elledge, an investigator at Howard Hughes Medical Institute in Chevy Chase, Md., and professor of genetics at Harvard Medical School in Boston. "You could get sick again from the same viruses you previously were immune to."

This immune system reset also hampers the body's ability to create antibodies against disease, meaning that new infections are likely to hit harder than before, according to a second team of researchers whose findings appear in the November issue of Science Immunology.

Both studies take their data from a 2013 measles outbreak in the Netherlands.

Families in communities with low vaccination rates agreed to provide blood samples, allowing researchers to observe the effects of a measles infection on non-vaccinated people.

Previous studies had suggested the effects of measles might persist long after infection, suppressing the immune system, Elledge said. But no one knew why that might be.

Analysis of blood from 77 unvaccinated Dutch children found the virus eliminated between 11-73 percent of their antibodies, Elledge's team found.

Antibodies are the cells that remember past encounters with pathogens and help the body avoid repeat infections.

"People had known that a lot of these immune cells get infected during measles, but they had no idea how much damage was being done," Elledge said.

The more severe a child's infection, the more it damaged their immune system, the researchers found.

"Those antibodies dropped precipitously. They went away very quickly," Elledge said. "This was really surprising. Nobody expected it to happen that quickly, because these kids had only been infected seven weeks ago."

The second team of researchers performed genetic sequencing on antibody genes from 26 Dutch children, before and then 40 to 50 days after their measles infection.

The investigators confirmed the loss of specific immune memory cells that had been built up against other diseases and had been present in the children's blood prior to measles.

The analysis showed the immune system had been reset to an immature state that could produce only a limited repertoire of antibodies, hampering the body's ability to respond to new infections.

Elledge said children could rebuild the immunity they had lost, but only by being exposed to infections again, or being vaccinated.

They also tested babies who had been vaccinated against measles — and found no decreases in their antibody levels — even though the vaccine contains live (but weakened) viruses. The vaccine virus is somewhat different from the natural one — and does not invade the crucial antibody-making cells.

Elledge said measles' effect on the immune system is similar to what a head injury does to the brain.

“If you’re in an accident and you injure your head, you could have some sort of amnesia and impaired function,” he said. “The measles virus is like an accident but for your immune system. It damages your immune system’s memory.”

In essence, the immune system forgets what it once knew, “sort of resetting the clock to an earlier more naïve stage of your life,” he said.

The measles vaccine, however, is like a seatbelt for the immune system and those who don’t vaccinate could face risks beyond measles infection, Elledge said.

“You’re rolling the dice and if you get unlucky you could get very sick from something that you should have been resistant to because you had the measles,” said Elledge.