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Thursday, October 31, 2019

How measles infections can wipe away immunity to other diseases

Measles wipes out some of the immunity to other diseases that children acquire through vaccinations and infections, leaving them more vulnerable to illness for months and even years afterward, two new studies published Thursday report.
The findings help explain why countries that start to vaccinate children against measles see pediatric death rates drop substantially, beyond just the decrease that would be expected with the prevention of measles deaths.
The first paper, published in Science, showed that children infected with measles lost between 11% and 73% of their antibodies after infection. The authors, from Harvard University, noted the children studied had been healthy and well-nourished before contracting measles, and the impact on malnourished children in parts of the developing world is likely greater still.
Peoples’ immune systems are like blackboards onto which immunological experiences — the antibodies they developed after contracting the flu or getting vaccinated against chickenpox and polio — are written. Measles infection erases big sections of the text, an effect sometimes called immune amnesia.
“The immune system forgot what it once knew,” said Stephen Elledge, senior author of the Science paper and a professor of genetics at Harvard Medical School.
The second paper, from researchers in Europe, was simultaneously published in the journal Science Immunology.
The damage isn’t to the immune system itself — it is still capable of producing antibodies to protect against threats it encounters after measles infection. But children who have had measles will lose some of the protection they had developed from any previous immunizations and infections.
Dr. Michael Mina, first author of the Harvard paper, said the phenomenon bears some similarities to the one that takes place after HIV infection. HIV also infects immune system cells.
“If you took the first 10 years of somebody having HIV and you squished that into a few weeks, that’s the kind of memory damage and immune damage you get from measles,” Mina, an assistant professor of epidemiology at Harvard’s T.H. Chan School of Public Health, told STAT.
“You have this really rapid [antibody] decline with measles, and then a slow increase,” he said. “Whereas with HIV you have essentially a slow decrease but you never return back to baseline without therapy.”
Paradoxically, measles infections generate a very strong immune response against measles in the future, one that in the vast majority of cases protects for a lifetime.
For years there have been questions about why measles vaccinations decreased childhood deaths overall, with some people arguing that the vaccine might actually be boosting existing immunity to other pathogens, even though it is designed to protect only against measles.
But there was skepticism about that explanation. And research done in animals showed the measles virus infects immune cells, killing some.
Mina thought the explanation needed to be turned on its head. It wasn’t that the vaccine was boosting overall immunity — it was preventing an infection that damaged the work the immune system had done to date.
“To me it seemed like a fairly obvious question to ask: Maybe it’s actually erasing immune memory?” he said.
In 2015 he and some colleagues published a paper in Science suggesting the effect is lasting. While the immune system’s functional ability bounces back pretty quickly after measles infection, it can take several years to re-establish the antibodies the infection wiped away.
The 2015 study was based on epidemiological data. In the new paper, Mina, Elledge, and colleagues used a tool Elledge’s lab developed — called VirScan — which actually detects thousands of types of antibodies and their targets.
Using the tool, they were able to show and quantify the damage measles infection inflicted, using blood samples from Dutch children from a religious community that did not vaccinate its children. Researchers in the Netherlands drew blood samples from the children during a 2013 measles outbreak, creating a valuable bank of before and after samples used by both groups that published Thursday.
The European work, led by Velislava Petrova of the Wellcome Sanger Institute at Cambridge University, looked at the effect of the measles on B cells, which generate antibodies. Stores of the cells, created in the bone marrow, were depleted by the virus — an effect, they said, that provides a biological explanation for why child deaths not related to the measles increase for several years after a measles outbreak.
Mina and Elledge both suggested doctors may want to consider re-vaccinating children and perhaps even adults who have been infected with measles. And the papers argue that this is further proof of the importance of broad use of measles vaccine.
Dr. Saad Omer, director of Yale University’s Institute for Global Health, said while the work is important, he is not certain it will sway people who object to vaccination. The measles vaccine is a particular target of the anti-vax movement.
“It may impact a few fence sitters, along with other messages,” said Omer. “But on its own I don’t think it would lead to a substantial change in perception.”
Omer said there is already a wealth of good science supporting the importance of measles vaccines and yet a small but vocal proportion of the population does not find it persuasive.

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