Inside Immune Amnesia

Study reveals how measles infection reduces protection against other diseases

Stephen Elledge stands at lab bench in front of window with tree visible outside
Authors Stephen Elledge and Michael Mina discuss the significance of their findings. Video: Rick Groleau and Ekaterina Pesheva

Over the last decade, evidence has mounted that the measles vaccine protects in not one but two ways: Not only does it prevent the well-known acute illness with spots and fever that frequently sends children to the hospital, but it also appears to protect from other infections over the long term.

How does this work?

Some researchers have suggested that the vaccine gives a general boost to the immune system.

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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.

However, many scientists still debate which hypothesis is correct. Among the critical questions are: If immune amnesia is real, how exactly does it happen, and how severe is it?

Now, a study from 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 provides much-needed answers.

Reporting Oct. 31 in Science, the researchers show that the measles virus wipes out 11 percent to 73 percent of the different antibodies that protect against viral and bacterial strains a person was previously immune to—anything from influenza to herpesvirus to bacteria that cause pneumonia and skin infections.

So, if a person had 100 different antibodies against chicken pox before contracting measles, they might emerge from having measles with only 50, cutting their chicken pox protection in half. That protection could dip even lower if some of the antibodies lost are potent defenses known as neutralizing antibodies.

“Imagine that your immunity against pathogens is like carrying around a book of photographs of criminals, and someone punched a bunch of holes in it,” said the study’s first author, Michael Mina, who was a postdoctoral researcher in the laboratory of Stephen Elledge at HMS and Brigham and Women’s at the time of the study and is now an assistant professor of epidemiology at the Harvard Chan School.

“It would then be much harder to recognize that criminal if you saw them, especially if the holes are punched over important features for recognition, like the eyes or mouth,” said Mina.

The 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 HMS and Brigham and Women’s. “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.”

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 Mina, who first discovered the epidemiological effects of measles on long-term childhood mortality in a 2015 paper.

The measles vaccine is of even greater benefit than we knew.

Stephen Elledge

White man with beard stands in front of a whiteboard covered in colorful schematics
In 2015, Stephen Elledge described what VirScan can reveal about human immunology and disease.
Kids on the edge—such as those with severe measles infection or immune deficiencies or those who are malnourished—will be in serious trouble.

Stephen Elledge