The measles outbreak in Texas, which has now spread to New Mexico, has infected mainly unvaccinated children. Of 159 cases, all but five were in unvaccinated individuals. One child has died. Cases have also been reported in six other states, including New York, New Jersey, and California. What has not been widely reported is what comes next for those who become infected: “exceptionally high rates of co-infections and hospitalizations for bacterial pneumonias and related conditions,” reports Michael Mina, a former assistant professor of immunology and infectious diseases at Harvard Medical School and of epidemiology at the Harvard T.H. Chan School of Public Health. This heightened vulnerability to other infections and diseases is particularly pronounced during the first two months following recovery. Although this corollary impact of measles has been known for years, it was thought to be caused by short-lived immune suppression—a temporary disabling of the ordinary immune response.
Between 2015 and 2019, however, Mina’s research proved that measles causes immune amnesia—when the immune system forgets how to fight off infections it successfully dealt with before—and showed that this effect lasts for years, not weeks or months. This leaves patients profoundly vulnerable to pathogens they have previously been vaccinated against or exposed to, and to which they would ordinarily be immune.
Mina’s first paper on the subject, an epidemiological study published in Science in 2015, used a large dataset of health information to reveal that children infected with measles continued to die at increased rates for years. At an individual level, this vulnerability was effectively invisible because “any functional immune test that you could throw at the kids a year after they got measles would look normal,” he explains. “So, the immune system appeared to be humming along, working normally.”
In 2019, when Mina was a postdoctoral fellow working with Mendel professor of genetics and medicine Stephen J. Elledge, a new technology allowed the researchers to see precisely what was happening in infected children. Using a tool called VirScan, which can sample a person’s complete immune history from a single drop of blood, they were able to show that increased mortality among children previously infected with measles did not result from suppressed or dysfunctional immune systems. Instead, Mina explains, “They had actually lost the memories that make up the immune system. That’s why we called it immune amnesia.”
“It’s very similar to what would happen if a concussion led you to forget an event in your life,” he continues. A test would show the brain working normally and able to form new memories. “But if the memory you forgot was really significant, like your wedding day, you’d be lacking something really important. And in the immune system, those important things are our immunological memories against pathogens.”
Why does measles have this effect while other infections do not? “Measles prefers to latch on to memory immune cells,” Mina says, “which is really distinct from every other virus.…That’s what makes measles really special.”
To spread throughout the immune system, measles uses a Trojan Horse mechanism. Normally, when a person breathes in a virus, dendritic cells in the lungs grab the pathogens, sequester them, and then carry them to the lymphoid tissue, where immune memories are made. This allows the immune system to destroy the pathogen and, crucially, to remember it. But in the case of measles, before that can happen, the virus latches onto a specific receptor—CD150—on the outside of immune cells, infects them, and replicates to infect even more cells. The virus thus enters “this very sacred space that it shouldn’t be in,” says Mina, “and that’s how the chain reaction begins,” leading to an explosion in viral load.
The infection is so profound that when researchers give monkeys fluorescently-labeled measles virus that makes their infected cells glow green, they can actually see, with the naked eye, the infected germinal centers where immune memories are formed and stored throughout a monkey’s body. “The houses of immune memory in the gut, the bone marrow, and the lymphatic tissue are just glowing green,” Mina explains, “and everything that’s green is just dying. That’s why measles has such a profound effect on immune memory.”
Does this mean people who have been vaccinated against measles should get a booster? Mina’s answer, based on as-yet-unpublished analyses of blood bank data, might be somewhat counterintuitive. Normally, as people age or as time passes after a vaccination, immunity wanes. But his research suggests that people who were vaccinated in the 1960s and 1970s may also have been exposed to measles in their daily lives, since the highly contagious virus was still circulating at the time. Such exposure likely served as a natural vaccine booster, conferring long-term immunity on many healthy individuals who are today in their 50s and 60s. At greater risk, he hypothesizes, are people who were vaccinated after measles was thought to have been eradicated. When someone born in the 1980s or 1990s reaches the age of 50 (or perhaps even 40), they might require a booster—and within the next decade, Mina predicts, public health recommendations will likely reflect that.
