Results from tests of unvaccinated children and monkeys come as measles cases spike around the world.
Children with measles receive care in a hospital in the Philippines.Credit: Ezra Acayan/Getty
Measles infections in children can wipe out the immune system’s memory of other illnesses such as influenza, according to a pair of studies1,2. This can leave kids who recover from measles vulnerable to other pathogens that they might have been protected from before their bout with the virus.
The findings, published on 31 October in Science and Science Immunology, come at a time when measles cases are spiking around the world. Globally, there were more measles infections in the first six months of 2019 than in any year since 2006, according to the World Health Organization.
The studies highlight the importance of measles vaccinations, says Michael Mina, an infectious-disease immunologist at the Harvard T. H. Chan School of Public Health in Boston, Massachusetts, and a co-author of the Science paper.
The measles virus is highly contagious, and can lead to complications including pneumonia. And previous studies have suggested that the virus induces a kind of forgetfulness in the immune system, says Duane Wesemann, an immunologist at Brigham and Women’s Hospital in Boston. When people get an infection, their immune system creates antibodies to fight it off. Once the body clears the infection, special immune cells remember that pathogen and help to mount a faster defence if the virus or bacterium invades again.
The Science study is the first to show definitive evidence that measles can destroy this immune memory, Mina says.
Inducing amnesia
Mina and his colleagues analysed blood samples from 77 unvaccinated children from 3 schools in the Netherlands, taken before and after a measles outbreak in 2013. The team also collected blood samples from 33 children before and after their first vaccination against measles, mumps and rubella (MMR). The researchers analysed the kids’ antibodies using a test that measures the amount, and the strength, of antibodies against thousands of viral and bacterial substances.
Two months after the unvaccinated children recovered from measles, the team found that the virus had erased 11–73% of their antibodies against other bacteria and viruses. Although the reasons behind the high variability in antibody reduction are unclear, the finding shows that the virus alters previously acquired immune memory, Mina says. The kids who received the MMR vaccine showed no reduction in these antibodies.
Mina and his team also infected macaques with measles and monitored the animals’ antibodies against other pathogens for five months. The monkeys lost 40–60% of their antibodies against previously-encountered pathogens, suggesting that the measles virus destroys otherwise-long-lived plasma cells in the bone marrow that can produce pathogen-specific antibodies for decades, Mina says.
Measles also seems to wipe out immune cells that ‘remember’ encounters with specific bacteria and viruses, according to a separate, independent team that published the Science Immunology study. When the scientists analysed blood samples from the same group of unvaccinated children in the Science study, the researchers found that those ‘memory’ cells had disappeared in the children who had contracted measles.
Unexpected protection
The findings emphasize how the MMR vaccine protects against more than just measles, says Velislava Petrova, an immunologist at the Wellcome Sanger Institute in Hinxton, UK, who led the Science Immunology study. It also prevents longer-term damage to the immune system that can lead to a resurgence of other diseases, she says.
It’s possible to rebuild someone’s suite of antibodies against specific bacteria and viruses by exposing them to those pathogens again, says Stephen Elledge, a geneticist at Harvard Medical School in Boston, and a co-author of the Science study. But some kids could develop life-threatening diseases as a result. “Every time you’re infected with a virus, that’s rolling the dice,” he says.
As immunization rates drop in some countries because of anti-vaccine campaigns and infrastructure problems, the findings from the two studies could help officials to develop more effective vaccination policies, says Akiko Iwasaki, a viral immunologist at Yale University in New Haven, Connecticut. “For me, that would be making sure vaccination is mandatory for children in public schools,” she says.
Clinicians could also consider giving people with measles a booster shot of vaccines they have previously received against other diseases, especially in regions where measles outbreaks are common, such as in sub-Saharan Africa, says Mina.
However various governments choose to address vaccinations, it’s crucial that countries prevent measles outbreaks by maintaining high vaccination rates against the virus, Mina says. “We have to do our best to ensure that measles remains on the elimination radar.”
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How measles causes the body to ‘forget’ past infections
Measles virus (blue) targets B cells, responsible for immune “memory.”
IMAGE: NIBSC/SCIENCE SOURCE
One of the most contagious human pathogens, the measles virus is dangerous enough by itself, with sometimes-fatal complications including pneumonia and brain inflammation. Two detailed studies of blood from unvaccinated Dutch children who contracted measles now reveal how such infections can also compromise the immune system for months or years afterward, causing the body to “forget” immunity it had developed to other pathogens in the past.
To what extent this “immune amnesia” increases illness and deaths from other infections isn’t clear. But the results are another good reason to immunize children against the virus, the studies’ authors and other infectious disease experts say. The findings are particularly sobering now that measles cases are increasing sharply—by more than 30% globally from 2017 to 2018—because of undervaccination and misguided vaccine safety concerns. “If we allow [measles] outbreaks to happen, we are knowingly creating pockets of people who are susceptible to other diseases as well,” says Velislava Petrova at the Wellcome Sanger Institute in Hinxton, U.K., who led one study.
“These two studies provide further strong evidence for the highly immunosuppressive effects of measles infection and the power of measles vaccination to counter it,” adds population biologist Bryan Grenfell of Princeton University, whose group in 2015 reported early evidence for the effect.
That finding was based on population data showing that mortality from other pathogens increases after a measles outbreak. Experiments in animals have also suggested the measles virus impairs immunity. So Petrova’s group and another, headed by Stephen Elledge of Harvard University, decided to explore this phenomenon more closely in people. Both teams chose a well-known cohort of children from an Orthodox Protestant community in the Netherlands whose parents had opted out of all vaccines for their children for religious reasons.
Michael Mina, a Harvard virologist who also worked on the population study, teamed up with Elledge to analyze blood samples from 77 of the children before and after they became infected during a 2013 measles outbreak in the Netherlands. Tomasz Kula, a postdoc in Elledge’s lab, had developed a technology called VirScan that enabled the team to test the antibodies in the infected children’s blood against antibody targets representing most known human pathogenic viruses.
Before the children contracted measles, their blood contained antibodies to many common pathogens. “These were really healthy kids,” Mina says. After the disease, the children lost, on average, about 20% of their antibody repertoire. Some fared much worse, losing more than 70% of their immunity to viral pathogens, the researchers report on p. 599 . They did not see the effect in their controls: five unimmunized children who never contracted measles over the course of the study, as well as more than 100 other children and adults. They also saw no loss of antibodies in children after they received a vaccination against measles.
The diminished antibody shield means that after a case of measles, unvaccinated children become vulnerable again to viruses they had been exposed to in the past. For example, if a child had contracted mumps prior to having measles, they might be susceptible to mumps again. “It’s like taking somebody’s immune system and rewinding time, putting them at a more naïve state,” Mina says.
To understand the effect, Petrova’s group did a different analysis of blood from the Dutch children. The team went straight to the source of antibodies: B cells, which the measles virus is known to infect. They found that measles infection reduced the diversity of memory B cells, which “remember” past infections and are quick to fight any recurrence. The virus killed off B cells specific to other pathogens, allowing new, measles-specific memory B’s to replace them.
Measles also decreased the diversity of another category of B cells: nonspecific naïve B cells in the bone marrow, which stand ready to fight unfamiliar infections. A measles infection left this cell repertoire “immature, similar to that of a fetus,” says Petrova, whose study appeared this week in Science Immunology. Basically, the measles virus doesn’t just delete immune memory—it makes it harder for the immune system to respond to new pathogens in the future.
“This [measles-induced immune amnesia] has never been characterized to the extent that they’ve done here,” says Mark Slifka, an immunologist at Oregon Health & Science University in Portland. But its long-term significance is unclear, he says, noting that immunity naturally fades as the body destroys some antibodies to keep their numbers in check. “Hopefully these families will be willing to continue to be involved with the researchers,” he says.
The only way to prevent measles from erasing immune memory, Mina says, is the obvious one: Prevent cases by vaccinating. In fact, Mina says, after a child has measles, physicians should consider revaccinating them against all common pathogens. “The Catch-22 is that [these children] are only getting measles because they’re not vaccinated in the first place,” he says.
On the other hand, says Jennifer Lighter, an infectious disease physician at New York University’s Langone Health in New York City, “I think after you see your child that has measles, you wouldn’t want your child to get other infections and to suffer needlessly.”
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