Measles wipes out other immune memories

By Dr. Ananya Mandal, MDNov 3 2019

Thanks to misinformation and anti-vaccination campaigns in some pockets, United States and several nations of Europe have seen a massive outbreak of vaccine preventable measles infection over the recent years. Now new research finds that measles infection weakens the immune system in its wake and leaves the individual prone to other infections. The measles vaccine thus not only protects an individual from measles but also boosts his or her long term immunity. The study was published in the latest issue of the Science (1) this week.

Measles viruses. 3D illustration showing structure of measles virus with surface glycoprotein spikes heamagglutinin-neuraminidase and fusion protein - Image Credit: Kateryna Kon / Shutterstock

Measles virus infection leads to rise in viral counts and fall in the lymphocyte counts in the body. The authors wrote, “Lymphocyte counts recover shortly after the disappearance of measles-associated rash, but immunosuppression can persist for months to years after infection, resulting in increased incidence of secondary infections.”

Researchers have found that measles virus can damage the immune system of the body and make it forget the microbes it knows. They explain, that the immune system acts as an army within the body. When they encounter a microbe – bacteria, or virus, it recognizes the organism and stores the memory of the bug. When the same microbe attacks again, the immune system from its memory rises to fight off the infection. This is the principle of a vaccine where the body is presented with a weakened or dead version of the microbe so that its memory of the organism is created. When a person is infected with measles, the virus can make the immune system forget its memories of other organisms as well. This is called immune-amnesia and makes a person vulnerable to infections he or she was earlier immune to.

According to evidence in scientific research measles virus can cause immune amnesia that can last for up to two to three years. The team from Harvard Medical School, Brigham and Women's Hospital and the Harvard T.H. Chan School of Public Health studied the effect of measles virus on the immune system in their latest study. They noted that measles virus is capable of erasing 11 to 73 percent of the memories of the immune system or antibodies that can protect the body against infections. For example, if a person has had chicken pox before, there is likelihood that he or she would not get the infection again. This could be because of the 100 different antibodies circulating within his or her body. The measles virus infection however could bring down the levels of these antibodies to half and that may raise the risk of his or her getting infected with chicken pox virus.

First author of the study, Michael Mina, formerly a postdoctoral researcher in the laboratory of Stephen Elledge at Harvard Medical School and Brigham and Women's Hospital and now an assistant professor of epidemiology at the Harvard T.H. Chan School of Public Health, said in a statement explaining, “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. 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.”

Lead author Stephen Elledge, the Gregor Mendel Professor of Genetics and of Medicine in the Blavatnik Institute at Harvard Medical School and Brigham and Women's Hospital added, “The threat measles poses to people is much greater than we previously imagined. 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.”

Mina had found in a study in 2015 that measles during childhood could significantly raise the risk of later illness and deaths. She said, “This is the best evidence yet that immune amnesia exists and impacts our bona fide long-term immune memory.”

In a related paper in the Science Immunology (2), titled, “Incomplete genetic reconstitution of B cell pools contributes to prolonged immunosuppression after measles,” lead author Velislava Petrova of the Wellcome Sanger Institute and team looked at the genes of the immune memory cells in the body to see the effects of the measles virus on these cells. Petrova said, “The immune cells that normally would recognize new pathogens — they become restricted in their ability to respond.” He added, “What was interesting is that we can recover our normal cell counts, but we're still immunosuppressed.”

In an accompanying editorial in the journal Science Immunology (3), written by Duane Wesemann, Harvard Medical School assistant professor of medicine at Brigham and Women's Hospital, put the present study in context of what was happening around the world – i.e. the measles outbreaks among the unvaccinated.

According to the researchers of the Science study, it may take a few years before the immune memories come back after a bout of measles infection. They add that this is an important consideration for physicians if they should provide a round of booster doses of vaccines for other infections such as polio and hepatitis to children who have had measles, in order to circumvent the immune amnesia. They wrote, “Revaccination following measles could help to mitigate long-term suffering that might stem from immune amnesia and the increased susceptibility to other infections.”

Elledge and Tomasz Kula, a PhD student in the Elledge Lab, had developed a tool called VirScan in 2015 that helped them understand the effects of the virus on the immune system in 2015. This tool helped detect the antibodies against the viruses and bacteria the immune system has previous encountered explained the researchers. Study author Rik de Swart, for this study obtained blood samples from children who had not been vaccinated in the 2013 outbreak of measles in Netherlands.

In the study the team used VirScan to measure the levels of the antibodies before a measles attack a two months after an attack of measles. They used 77 samples from infected children for their experiment and compared them with 115 samples from children and adults who had never had measles. According to Kula, there was a sharp drop in the antibodies for other microbes in the blood of the measles infected children and this showed the effect of the measles virus on the immune system. Elledge said, “This proved to be the first definitive evidence that measles affects the levels of protective antibodies themselves, providing a mechanism supporting immune amnesia.” The authors wrote, “Memory B cell clones present before infection were depleted in post-measles samples even after lymphocyte counts had recovered.”

Following this the team then worked with Diane Griffin at Johns Hopkins Bloomberg School of Public Health and measured the levels of antibodies four rhesus macaques or monkeys. The levels of antibodies were measured before measles infection and five months after it. Macaques are similar to humans and thus this longer time study yielded results that were more robust explain the researchers. The results showed that the macaques also lost an average of 40 to 60 percent of the antibodies to the viruses and bacteria that the monkeys were exposed before.

The team warned that this loss of the immune system after measles infection could be a particular danger for some populations of children and adults. For example among malnourished children and children and adults with immune deficiency, the risk is greater. Elledge said, “The average kid might emerge from measles with a dent in their immune system and their body will be able to handle that. 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.”

Mina said in conclusion, “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. 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.”

Wesemann who wrote the accompanying editorial said, “You get the best of both worlds with the vaccine.” He added, “You get the robust immunity against measles virus without having to be infected with it, but it doesn't cause the immune damage that the real measles virus causes. The measles vaccine is really a superhero.”