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Saturday, 2 November 2019

Measles clears some of the immune memory, preventing the body from fighting other infections


Measles is a highly contagious viral infection that usually affects young children. Although the main symptoms may at first seem relatively benign, the virus can spread to the brain or lungs, leading to dangerous life-threatening complications such as encephalitis or pneumonia. In two recent studies, virologists have shown that measles clears some of the body's immune memory, preventing it from fighting infections during or after the disease, even though the patient had already faced to these infections before.

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Once infected, the amnesic immune system no longer recognizes the pathogens it has fought in the past. This means that measles survivors can remain exposed to dangerous diseases - such as influenza and pneumonia - for years, even though they have overcome their initial illness.

" Measles essentially removes their ability to protect themselves effectively, " says Michael Mina, an epidemiologist at Harvard University and co-author of the new study published in the journal Science . The article is associated with another published in the journal Science Immunology .

Using data from a group of unvaccinated children in the Netherlands, both studies revealed what virologists suspected for a long time: the measles virus paralyzes the immune system in a deep and lasting way.

" This work specifies exactly how immunosuppression occurs, and gives us an idea of ​​the magnitude of the immunosuppression in question," says William Schaffner, Professor of Preventive Medicine and Infectious Diseases at Vanderbilt University. The results also point out that this year's record measles outbreaks in the United States will have lingering effects.

Measles is an infectious disease transmitted by a morbillivirus of the family Paramyxoviridae . It manifests itself in many symptoms and can lead to serious complications. Credits: CDC / WHO

These children are currently going through a post-measles period more exposed to other infections ." According to the World Health Organization, the number of measles cases has increased by more than 280% since 2018, which means that hundreds of thousands of people who have caught the virus this year could now also be infected. secondary.

Suppression of some of the body's immune memory

Virologists have long believed that the measles virus can cause "immune amnesia," but the underlying mechanism remains unclear. They know that once the virus has infected a person, it reduces the reserves of white blood cells that kill pathogens. The number of immune cells returns to normal levels once the infection is eliminated, but even then the affected person may remain immunocompromised for years.

" But paradoxically, it leaves a solid immunity to measles, " said Duane Wesemann, a professor of medicine at Brigham and Women's Hospital. In other words, while measles survivors struggle to defend themselves against other pathogens, their bodies can prevent a new attack from the measles virus itself.

In fact, before the introduction of the measles vaccine in the 1960s, about 50% of child deaths could have been associated with infections they contracted after surviving a measles crisis, according to a 2015 study released in the journal Science . How, then, does measles cause such damage to the immune system even after the disappearance of the infection?

To find out, the authors of the new articles took blood samples from 82 unvaccinated Dutch children. In a measles outbreak that hit the country in 2013, five of the children managed to avoid infection but most caught the virus. The authors compared blood samples taken from children before and after infection to determine the evolution of their immune system.

Massive loss of B-cells after measles infection

The authors of the Science Immunolog study examined the white blood cells of children, including a type of white blood cell called B cells. When the body detects a new pathogen, B cells produce proteins that target the germ and transmit it. to another protein for destruction. B cells continue to develop these antibodies even after the pathogen disappears, so the body remembers the disease if it should return.

Graphs showing the loss of B and T lymphocytes during infection. B-lymphocytes constitute an acquired immune memory; their loss thus means a disappearance of this immune memory. Credits: Velislava N. Petrova et al. 2019

The researchers found that children infected with the measles virus lose many B-cells trained to recognize common infections.

Forty to fifty days after infection, once the virus is eliminated, the affected children have assembled a new army of B cells to replace those lost during the disease. However, the effectiveness of these in the fight against specific infections is not yet determined - this could be a question for future studies, according to Wesemann.

Antibodies: they partially disappear during infection

Rather than take stock of B cells, the authors of the study published in Science have looked directly at the first line of the immune defense: the antibodies themselves. Trillions of antibodies can be found in every microliter of blood. Many of these antibodies are produced by bone marrow cells called "long-lived plasma cells", which also perish because of the measles virus.

Using a tool called VirScan, researchers determined which antibodies appeared in the blood of children before and after measles. The screening tool allowed researchers to go through the children's medical history and see what pathogens they had encountered in their lifetime. But the measles virus has erased much of this story.

Graph showing the loss of antibodies (in red) during measles infection, compared to control groups (gray and green). Credits: Michael J. Mina et al. 2019

After catching the virus, children lost between 11% and 72% of their total antibody diversity, indicating that measles had partially erased their immune memory. In general, the number of antibodies lost seems to depend on the severity of the measles infection. Vaccinated children, as well as unimmunized individuals who did not contract measles, retained approximately 90% of their antibody repertoire during the same period.

Re-enter pathogens to rebuild immune memory

Measles survivors can recover from immune amnesia, but only by re-familiarizing themselves with all their previous pathogens. In the Science study , some children quickly recovered new antibodies to fight against staphylococcal infections, influenza and adenoviruses, the family of viruses that cause sore throats and pneumonia.

The researchers found that all these children lived together or in the same neighborhoods, which accelerated the spread of pathogens. " What we were actually attending was the re-education of their immune system, " says Mina. Although healthy Dutch children have resisted these secondary infections, malnourished or immunosuppressed children may not be able to cope as well after measles.

Vaccine against measles: the best defense against disease

Wesemann wondered whether antibody replacement therapy, in which people received antibodies from donors, could help maintain children's immune systems after measles infection, while strengthening their defenses. Questions also remain about why some children lose more measles antibodies than others and how the evolution of white blood cell diversity affects survivors.

One thing is clear: the measles vaccine is fantastic. It endows the body with an arsenal of anti-measles antibodies, just like the virus itself. But unlike infection, inoculation does not diminish the body's ability to build antibodies against other pathogens. You get all the benefits and no inconvenience with the vaccine, "Wesemann concludes.

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