Measles Infection Causes "Immune Amnesia" by Attacking Antibodies

Measles infections take a toll on the body’s immune system, wiping out 11% to 73% of antibodies to various viral and bacterial pathogens, according to a new study by an international team of investigators at Harvard Medical School, Brigham and Women’s Hospital and the Harvard T.H. Chan School of Public Health.

In the study, published in Science, investigators used the VirScan assay to examine the antibodies of 77 unvaccinated children in the Netherlands before and after measles infections. Children in the study who had severe measles infections lost an average of 40% of their total preexisting pathogen-specific antibody repertoires and those with mild measles infections lost an average of 33%. Those in control groups retained about 90% of their antibodies.

“The threat measles poses to people is much greater than we previously imagined,” senior author Stephen Elledge, PhD, the Gregor Mendel Professor of Genetics and of Medicine in the Blavatnik Institute at Harvard Medical School and Brigham and Women’s Hospital, said in a news release. “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.”

VirScan is phage-display immunoprecipitation and sequencing (PhIP-Seq) technology that detected changes to neutralizing and non-neutralizing antibodies. Investigators developed an epitope binding signal (EBS) to measure relative antibody titers. The average decrease was about 31% across all species for those who had been infected with measles.

The study, which is the first to measure immune damage caused by measles infections, determined that the measles, mumps, rubella vaccine did not result in a similar reduction in antibodies.

“This is the best evidence yet that immune amnesia exists and impacts our bona fide long-term immune memory,” Michael Mina, MD, PhD, a postdoctoral researcher at the time of the study who is now assistant professor of epidemiology at the Harvard T.H. Chan School of Public Health, said in the news release.

The study found that recovery of antibodies was high for some pathogens, such as adenovirus C, influenza A virus, respiratory syncytial virus, human herpesvirus, Streptococcus pneumoniae and Staphylococcus aureus, and that increase was associated with new exposures. Regaining immunity could take months to years, and leave patients vulnerable to dangerous infections. Investigators suggested booster shots of all previous routine vaccines after measles infection.

Investigators confirmed the findings with an examination of measles infection in four rhesus macaques, finding that each money lost an average of 40% to 60% of its preexisting antibody repertoire, which persisted for at least 5 months.

Another study published in Science Immunology reached a similar conclusion about immune amnesia by measuring changes in B cells after measles infection.

These studies suggest that the overall mortality rate attributable to measles could be much higher than previously estimated and that vaccination could prevent not only deaths from measles infection — estimated to be about 120,000 worldwide this year alone — but also hundreds of thousands of deaths from infections due to the resulting weakened immune systems. The issue could be more severe among less healthy populations, such as those with immune deficiencies or who are malnourished.

Measles has been declared eliminated in the United States but that status has been threatened as the disease has begun to make a comeback. A record number of cases of infection — 1,250 — were confirmed in 31 states from January 1 through October 3 this year. About 75% of this year’s cases were linked to outbreaks in New York.

The World Health Organization has classified measles as a Grade 2 emergency in Europe, where four countries lost their measles elimination status this year and 12 remain endemic for measles. Vaccine hesitance was listed by the World Health Organization among the top global health threats of 2019.