Measles wipe out the body's immune memory!

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.

Some researchers have suggested that the vaccine gives a general boost to the immune system.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 provides much-needed answers. Reporting 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. "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 the author.

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 discovery that measles depletes people's antibody repertoires, partially obliterating immune memory to most previously encountered pathogens, supports the immune amnesia hypothesis. The team's current work was published simultaneously with a paper by a separate team in Science Immunology that reached complementary conclusions by measuring changes in B cells caused by the measles virus.

The authors found that those who survive measles gradually regain their previous immunity to other viruses and bacteria as they get re-exposed to them. But because this process may take months to years, people remain vulnerable in the meantime to serious complications of those infections.

In light of this finding, the researchers say clinicians may want to consider strengthening the immunity of patients recovering from measles infection with a round of booster shots of all previous routine vaccines, such as hepatitis and polio.

"Revaccination following measles could help to mitigate long-term suffering that might stem from immune amnesia and the increased susceptibility to other infections," the authors said.

This new discovery was made possible thanks to VirScan, a tool the lab developed in 2015.VirScan detects antiviral and antibacterial antibodies in the blood that result from current or past encounters with viruses and bacteria, giving an overall snapshot of the immune system.

Study co-author had gathered blood samples from unvaccinated children during a 2013 measles outbreak in the Netherlands. For the new study, the group used VirScan to measure antibodies before and two months after infection in 77 children from de Swart's samples who'd contracted the disease. The researchers also compared the measurements to those of 115 uninfected children and adults.

When the authors examined an initial set of these samples, they found a striking drop in antibodies from other pathogens in the measles-infected children that "clearly suggested a direct effect on the immune system," the authors said.

The effect resembled what they had hypothesized could drive measles-induced immune amnesia."This proved to be the first definitive evidence that measles affects the levels of protective antibodies themselves, providing a mechanism supporting immune amnesia," said the senior author.

Then the team measured antibodies in four rhesus macaques--monkeys closely related to humans--before and five months after measles infection. This covered a much longer period post-infection than what was available in the Netherlands samples.

Similar to the findings in people, the macaques lost an average of 40 to 60 percent of their preexisting antibodies to the viruses and bacteria they had been previously exposed to.
Further tests revealed that severe measles infection reduced people's overall immunity more than mild infection. This could be particularly problematic for certain categories of children and adults, the researchers said.

The authors stress that the effects observed in the current study occurred in previously healthy children. Because measles is known to hit malnourished children much harder, the degree of immune amnesia and its effects could be even more severe in less healthy populations.

"The average kid might emerge from measles with a dent in their immune system and their body will be able to handle that," said the senior author. "But kids on the edge--such as those with severe measles infection or immune deficiencies or those who are malnourished--will be in serious trouble."

Inoculation with the MMR (measles, mumps, rubella) vaccine did not impair children's overall immunity, the researchers found. The results align with decades of research.

Ensuring widespread vaccination against measles would not only help prevent the 120,000 deaths that will be directly attributed to measles this year alone but could also avert potentially hundreds of thousands of additional deaths attributable to the lasting damage to the immune system, the authors said.

"This drives home the importance of understanding and preventing the long-term effects of measles, including stealth effects that have flown under the radar of doctors and parents," said the first author. "If your child gets the measles and then gets pneumonia two years later, you wouldn't necessarily tie the two together. The symptoms of measles itself may be only the tip of the iceberg."

https://hms.harvard.edu/news/inside-immune-amnesia