An international team of researchers led by investigators at Harvard Medical School, Brigham and Women’s Hospital and the Harvard T.H. Chan School of Public Health found that the measles virus wipes out 11 to 73 percent of the different antibodies that protect against viral and bacterial strains a person was previously immune to—anything from influenza to herpes viruses to bacteria that cause pneumonia and skin infections.
Their study is the first to measure the immune damage caused by the virus and underscores the value of preventing measles infection through vaccination, the authors said.
“The threat measles poses to people is much greater than we previously imagined,” said senior author Stephen Elledge, the Gregor Mendel Professor of Genetics and of Medicine in the Blavatnik Institute at Harvard Medical School and Brigham and Women’s Hospital. “We now understand the mechanism is a prolonged danger due to erasure of the immune memory, demonstrating that the measles vaccine is of even greater benefit than we knew.”
Some researchers have suggested that the vaccine gives a general boost to the immune system. Others have hypothesized that the vaccine’s extended protective effects stem from preventing measles infection itself. According to this theory, the virus can impair the body’s immune memory, causing so-called immune amnesia. By protecting against measles infection, the vaccine prevents the body from losing or “forgetting” its immune memory and preserves its resistance to other infections. Past research hinted at the effects of immune amnesia, showing that immune suppression following measles infection could last as long as two to three years.
The discovery that measles depletes people’s antibody repertoires, partially obliterating immune memory to most previously encountered pathogens, supports the immune amnesia hypothesis.
“This is the best evidence yet that immune amnesia exists and impacts our bona fide long-term immune memory,” added the study’s first author Michael Mina, a postdoctoral researcher in the laboratory of Stephen Elledge at the time of the study and now an assistant professor of epidemiology at the Harvard T.H. Chan School of Public Health. Mina first discovered the epidemiological effects of measles on long-term childhood mortality in a 2015 paper.
The team’s current work was published simultaneously with a paper by a separate team in Science Immunology that reached complementary conclusions by measuring changes in B cells caused by the measles virus. An accompanying editorial in Science Immunology, written by Duane Wesemann, Harvard Medical School assistant professor of medicine at Brigham and Women’s Hospital, contextualizes that study.
Elledge, Mina and colleagues found that those who survive measles gradually regain their previous immunity to other viruses and bacteria as they get re-exposed to them. But because this process may take months to years, people remain vulnerable in the meantime to serious complications of those infections.
In light of this finding, the researchers say clinicians may want to consider strengthening the immunity of patients recovering from measles infection with a round of booster shots of all previous routine vaccines, such as hepatitis and polio.
“Revaccination following measles could help to mitigate long-term suffering that might stem from immune amnesia and the increased susceptibility to other infections,” the authors said.
One of the most contagious diseases known to humankind, measles killed an average of 2.6 million people each year before a vaccine was developed, according to the World Health Organization (WHO). Widespread vaccination has slashed the death toll.
However, lack of access to vaccination and refusal to get vaccinated means measles still infects more than 7 million people and kills more than 100,000 each year worldwide, reports the WHO—and cases are on the rise, tripling in early 2019. About 20 percent of people in the U.S. who get infected with measles require hospitalization, according to the Centers for Disease Control and Prevention (CDC), and some experience well-known long-term consequences, including brain damage and vision and hearing loss.
Previous epidemiological research into immune amnesia suggests that death rates attributed to measles could be even higher—accounting for as much as 50 percent of all childhood mortality—if researchers factored in deaths caused by infections resulting from measles’ ravaging effects on immunity.
This new discovery was made possible by VirScan, a tool Elledge and Tomasz Kula, a PhD student in the Elledge Lab, developed in 2015. VirScan detects antiviral and antibacterial antibodies in the blood that result from current or past encounters with viruses and bacteria, giving an overall snapshot of the immune system.
Study co-author Rik de Swart had gathered blood samples from unvaccinated children during a 2013 measles outbreak in the Netherlands. For the new study, Elledge’s group used VirScan to measure antibodies before and two months after infection in 77 children from de Swart’s samples who’d contracted the disease. The researchers also compared the measurements to those of 115 uninfected children and adults.
When Kula examined an initial set of these samples, he found a striking drop in antibodies from other pathogens in the measles-infected children that “clearly suggested a direct effect on the immune system,” the authors said. The effect resembled what Mina had hypothesized could drive measles-induced immune amnesia.
Then, in collaboration with Diane Griffin at Johns Hopkins Bloomberg School of Public Health, the team measured antibodies in four rhesus macaques — monkeys closely related to humans — before and five months after measles infection. Similar to the findings in people, the macaques lost an average of 40 to 60 percent of their preexisting antibodies to the viruses and bacteria they had been previously exposed to.
Further tests revealed that severe measles infection reduced people’s overall immunity more than mild infection. This could be particularly problematic for certain categories of children and adults, the researchers said.
The authors stress that the effects observed in the current study occurred in previously healthy children. Because measles is known to hit malnourished children much harder, the degree of immune amnesia and its effects could be even more severe in less healthy populations. Inoculation with the MMR (measles, mumps, rubella) vaccine did not impair children’s overall immunity, the researchers found. The results align with decades of research.
