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Measles virus deletes part of human immune system memory, finds Wellcome Sanger Institute

The measles virus deletes part of the memory in our immune systems, leaving us susceptible to other infections, Wellcome Sanger Institute researchers and their collaborators have found.

For the first time, they have shown that measles resets human immune systems back to an immature baby-like state that has limited power to respond to new threats.

Dr Velislava Petrova, of the Wellcome Sanger Institute and Cambridge University. Picture: Philip Mynott (20654842)
Dr Velislava Petrova, of the Wellcome Sanger Institute and Cambridge University. Picture: Philip Mynott (20654842)

The study, reported in Science Immunology, has important implications as vaccination rates in the country are falling.

This is leading to a rise in the number of cases of measles – an infection that can be deadly in itself – and could also lead to a growing number of cases of other dangerous infections, such as flu, diphtheria or tuberculosis, even in people who were previously immune.

Dr Velislava Petrova, lead author from the Wellcome Sanger Institute and the University of Cambridge, said: “This study is a direct demonstration in humans of ‘immunological amnesia’, where the immune system forgets how to respond to infections encountered before. We show that measles directly causes the loss of protection to other infectious diseases.”

The work by researchers at the Sanger Institute, University of Amsterdam and their collaborators explains why children often catch other infectious diseases after measles.

The measles virus causes coughing, rashes and fever. It can also lead to potentially fatal complications such as pneumonia and encephalitis, which causes inflammation of the brain. More than 100,000 deaths are caused by measles worldwide each year in unvaccinated communities, according to the World Health Organisation (WHO).

In 1968, a very effective measles vaccine was introduced in the UK. Administered in two doses at age one and three as part of the MMR vaccine – which also protects against mumps and rubella – government figures indicate it has saved an estimated 20million measles cases and 4,500 deaths.

In 2017, the UK was declared a measles-free country.

But the WHO withdrew the country’s measles elimination status in 2018, when 1,250 cases were recorded – many of them among young people aged 15 and over who missed out on the MMR vaccination when they were younger.

Statistics on measles (24050725)
Statistics on measles (24050725)

Most UK cases have been linked to travel in Europe, where there were more than 82,500 measles cases in 2018 – three times as many as in 2017 and 15 times as many as in 2016.

While scientists have known that measles weakens the immune system, even after the initial infection cleared, they have not known how – until now.

In measles patients, the number of white blood cells – immune cells that protect against infection – falls, giving a low white blood cell count in tests. But this count returns to previous levels after recovery, only for patients to remain much more susceptible to infectious diseases.

To find out why, researchers took blood from healthy non-vaccinated volunteers in the Netherlands, and repeated the sampling after a measles outbreak in 2013.

Sequencing antibody genes from 26 children, before and 40 to 50 days after their measles infection, the researchers discovered specific immune memory cells that had been built up against other diseases had disappeared, leaving them vulnerable.

The scientists tested this ‘immunological amnesia’ in ferrets, showing that infection with a measles-like virus reduced the level of influenza antibodies in ferrets previously vaccinated against flu. The ferrets also had worse flu symptoms when infected with the flu virus after the measles-like infection.

Professor Paul Kellam, an author on the paper from Imperial College London, and previously from the Wellcome Sanger Institute, said: “We showed that measles-like viruses can delete pre-existing flu immune memory from ferrets.

Measles can leave us susceptible to other infections (24050723)
Measles can leave us susceptible to other infections (24050723)

“Even after the ferrets had been successfully vaccinated against flu, the measles-like virus reduced levels of flu antibodies, resulting in the animals becoming susceptible to flu infection again and experiencing more severe flu-like symptoms.

“This shows that measles could reverse the effects of vaccination against other infectious diseases.”

The study concluded that the measles virus leaves the immune system in an immature state, which is only able to make a limited repertoire of antibodies against disease.

Prof Colin Russell, senior author from the University of Amsterdam, in the Netherlands, said: “For the first time we see that measles resets the immune system and it becomes more baby-like, limiting how well it can respond to new infections.

“In some children the effect is so strong it is similar to being given powerful immunosuppressive drugs.

“Our study has huge implications for vaccination and public health as we show that not only does measles vaccination protect people from measles, but also protects from other infectious diseases.”

The work illustrates how genetic techniques can reveal mechanisms of disease undetectable from routine tests.

Signs of immune supression have been found in some children for up to five years after measles, even though their white blood cell counts has returned to normal.

Dr Charlie Weller, head of vaccines at Wellcome, said: “Measles is highly contagious and its potentially devastating consequences are well known.

The MMR jab protects against measles, mumps and rubella (24050721)
The MMR jab protects against measles, mumps and rubella (24050721)

“This study finds that measles also has the potential to weaken our body’s existing immune response to other diseases, leaving us vulnerable to infections.

“These findings further strengthen the vital role the MMR vaccine plays in public health and protecting us from deadly disease.

“It is yet another reminder of how important vaccines are as a vital resource in eliminating infectious disease.”

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