Issue: December 2019
November 04, 2019
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Measles causes ‘immune amnesia,’ leaving patients vulnerable to repeat infections

Issue: December 2019
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Paul Offit
Paul A. Offit

Two studies investigating the immune systems of unvaccinated children in the Netherlands demonstrated that measles virus can give patients “immune amnesia” — that is, it erases the immune system’s memory of past encounters with other pathogens, leaving them vulnerable to future infections.

“These findings are not surprising,” Paul A. Offit, MD, director of the Vaccine Education Center and attending physician at Children’s Hospital of Philadelphia, told Infectious Disease News. “It’s biologically plausible because natural measles virus can reproduce itself in dendritic cells, which are antigen-presenting cells. There is a biological basis for why it is that measles would cause immune amnesia.”

But Offit, who was not involved in either study, said the findings add a broader definition of immune system paralysis to the literature, and show that the immune system is broadly affected by natural measles, which is consistent with “what is known about the clinical disease.”

“Yet another arrow in the quiver for pediatricians who are trying to talk about the importance of preventing measles infections,” he said.

Measles eliminates protective antibodies

In the first study, Michael J. Mina, MD, PhD, assistant professor of epidemiology at the Harvard T.H. Chan School of Public Health, and colleagues found that measles eliminated between 11% and 73% of protective antibodies, suggesting that it may destroy the immune system.

The study was based on an analysis of antibody response before and after measles infection in 77 unvaccinated children using VirScan, “a powerful pathogen antibody profiling technology” developed by co-author Stephen J. Elledge, PhD, professor of medicine at Harvard Medical School, in 2015.

Using epidemiological and population data, Mina and colleagues previously showed that children who had measles were at an increased risk for infection 2 to 3 years following the illness. Those findings, combined with what is already known about how measles infects the body, “pointed strongly toward an immunological effect underlying the process,” according to Mina and Elledge. However, until now, there were no biological data to explain the findings.

“This study is the first to detect that measles erases a large portion of the protective immunological long-term memory that individuals have developed over their lifetime prior to becoming infected with measles,” Mina and Elledge told Infectious Disease News.

Peter Hotez, MD, PhD, FASTMH, FAAP, dean of the National School of Tropical Medicine and professor of pediatrics at Baylor College of Medicine, called the findings “significant.”

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“Up until recently measles has been one of the great killers of children globally because of its major complications — measles pneumonia and encephalitis. In 2019, measles returned to the United States causing a serious epidemic in New York that resulted in 50 hospitalizations, including 18 ICU admissions,” Hotez, who was not involved in either study, told Infectious Disease News. “The study adds to our urgency the importance of global efforts to eliminate measles and to refute a major assertion by the antivaccine lobby that measles is just a rash or a benign illness.”

‘Unique relationship’

Peter Hotez
Peter Hotez

In the second study, Velislava N. Petrova, PhD, a postdoctoral fellow at the Wellcome Sanger Institute, and colleagues sequenced antibodies produced by B cells in the same population of unvaccinated children and compared the B cell data from before and after measles infection. They discovered that the restocking of the B cell pool was incomplete, and the depletion of B cell clones compromised immune memory.

According to Mina and Elledge, they assumed that antibodies would be lost. But the findings were still surprising because of “the sheer magnitude and range of the loss of the long-term immune antibody memory.”

The findings provide the “needed biological evidence” of the long-term impact measles has on immunity.

“It should serve to help urge for continued efforts toward measles prevention and elimination through maintenance of high levels of measles vaccination,” they said.

In a related editorial, Duane R. Wesemann, MD, PhD, assistant professor of medicine at Brigham and Women's Hospital in Boston, underscored the efficacy of vaccination and its importance as a public health intervention, as well as the critical need to continue to study measles.

“Although a proven childhood vaccine to protect humans from measles has been available for years, the studies by Petrova and colleagues and Mina and colleagues represent an opportunity to examine the measles virus against the Delphic maxim to ‘know thyself’ — because the unique relationship measles has with the human immune system can illuminate aspects of its inner workings,” he wrote. – by Marley Ghizzone

References:

Mina MJ, et al. Science. 2019;doi:10.1126/science.aay6485.

Petrova VN, et al. Sci Immunol. 2019;doi:10.1126/sciimmunol.aay6125.

Wesemann DR, et al. Sci Immunol. 2019;doi:10.1126/sciimmunol.aaz4195.

Disclosures: Elledge reports founding MAZE Therapeutics, Mirimus and TSCAN Therapeutics, and serving on the scientific advisory boards of CRISPR Therapeutics, Homology Medicines, TSCAN Therapeutics, and XChem and to being an adviser for MPM Capital. Mina reports serving as a member of a Sanofi advisory board for RSV therapeutics. Please see the study for all other authors’ relevant financial disclosures. Wesemann reports receiving grant support from the NIH and a Career Award for Medical Scientists from the Burroughs Wellcome Fund, and consulting for OpenBiome. Hotez, Offit, and Petrova and colleagues report no relevant financial disclosures.