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Measles infection linked to impaired ‘immune memory’

Key clinical point: Children infected with measles may have reduced immunity to other pathogens with which they have previously been infected.

Major finding: Children who get infected with the measles virus show approximately a 20% mean reduction in antibody repertoire.

Study details: A study in 77 unvaccinated children infected with measles and 5 unvaccinated, uninfected controls; a genetic investigation of 26 unvaccinated children from the Netherlands who previously had measles.

Disclosures: The study by Mina et al. was supported by grants from various U.S., European, and Finnish foundations and national organizations. Some of the coauthors had relationships with biotechnology and pharmaceutical companies, and three declared a patent holding related to technology used in the study. The study by Petrova et al. was funded by grants to the investigators from various Indonesian and German organizations and the Wellcome Trust. The authors reported no conflicts of interest.

Citation:

Mina M et al. Science. 2019 Nov 1;366:599-606; Petrova VN et al. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aay6125.

Commentary:

As a result of reduced vaccination, after decades of decline, the number of worldwide cases of measles has increased by nearly 300% since 2018. Epidemiologic evidence has associated measles infections with increases in morbidity and mortality for as long as 5 years after the infection and suggests that, in the prevaccine era, measles virus may have been associated with up to 50% of all childhood deaths, mostly because of nonmeasles infections. Measles replication in immune cells has been hypothesized to impair immune memory, potentially causing what some scientists call “immunological amnesia.”A measles virus receptor, called CD150/ SLAMF1, is highly expressed on memory T, B, and plasma cells. Measles virus gains entry to these immune memory cells using that receptor and kills the cells.

In a remarkable study by Mina et al. published in Science, the impact of the phenomenon called immunologic amnesia was studied in a group of unvaccinated children who experienced natural measles infection, compared with unimmunized children who were not infected. The scientists used a cutting-edge technology to measure the antibody repertoire in blood to most known human pathogenic viruses (approximately 400 species and strains) plus many bacterial proteins. Changes in pathogen-specific antibodies measured in the peripheral blood reflect changes in the long-lived plasma cells (LLPCs) that live in the bone marrow and provide immune memory. Astonishingly, after mild or severe measles, children lost a median of 33% (range, 11%-62%) or 40% (range, 12%-73%), respectively, of their total preexisting pathogen-specific antibody repertoires. Because LLPCs do not replicate, the rebuilding of immune memory after measles-induced LLPC elimination would likely require reexposures, either through natural infection or vaccination. The paper also described testing of children who received measles vaccination and showed vaccination had no adverse effect on preexisting antibody repertoire.

The scientists stated that it could take months or years to return the immune repertoire back to baseline. During the rebuilding process, children would be at increased risk for infectious diseases they had previously experienced.

In a second outstanding paper, Petrova et al. in Science Immunology studied B cells before and after measles infection, and identified two immunologic consequences: The naive B-cell pool was depleted, leading to a return to immunologic immaturity, and the memory B-cell pool was depleted, resulting in compromised immune memory to previously encountered pathogens.

Thus, the link between measles infections and increased susceptibility to other infections and increased deaths from nonmeasles infectious diseases in the aftermath of measles has been revealed. This information adds new data to share with parents who consider refusing measles vaccination. The risks are far greater than getting measles.

Michael E. Pichichero, MD, is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He was asked to comment on the articles. Dr. Pichichero has no conflicts to declare.