Measles virus (blue) targets B cells, responsible for immune “memory.”

NIBSC/SCIENCE SOURCE

How measles causes the body to ‘forget’ past infections by other microbes

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 this week in Science. 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."