NEW YORK – Children's immune systems may be less adept at staving off new infectious diseases after a measles virus infection due to "immune amnesia," according to new research from investigators at the Wellcome Sanger Institute, University of Amsterdam, and elsewhere.
"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," co-senior author Colin Russell, an applied evolutionary biology researcher at the University of Amsterdam said in a statement. "In some children the effect is so strong it is similar to being given powerful immunosuppressive drugs."
As Russell and his colleagues reported online yesterday in Science Immunology, the researchers used targeted sequencing to follow blood samples from more than two-dozen children prior to measles infections and again more than a month after the infections cleared. The sequence data pointed to decline in immune memory cells and B lymphocyte white blood cell diversity following measles infections — results that lined up with those found in influenza-exposed ferret infection models.
Based on their findings, the study's authors stressed the importance of maintaining and improving measles vaccination programs to prevent problematic measles infections, particularly since there were hints from the ferret experiments that the measles infections might actually dial down the effectiveness of vaccines against other infectious agents or to diseases encountered already.
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," Russell said.
Measles were thought to be eliminated in the UK by 2017, the team explained. But cases have started to return in the UK as vaccination rates decline. The disease — marked by symptoms ranging from a cough, fever, and rash to potentially fatal secondary infections — involves a rise in viral levels in the blood coupled with waning white blood cell representation.
"Lymphocyte counts recover shortly after the disappearance of measles-associated rash," the authors noted, "but immunosuppression can persist for months to years after infection, resulting in increased incidence of secondary infections."
In an effort to untangle the specific immune cell changes involved in this process, the researchers did isotype-resolved B-cell receptor sequencing to barcode and follow immune cells in peripheral blood samples collected at baseline in 26 unvaccinated children from a study in the Netherlands, and again some 40 to 50 days after their measles virus infections.
Using sequence clues, the team extrapolated antibody; naïve B cell and memory B lymphocyte profiles; and other immune patterns, comparing them with those in samples from unvaccinated children who dodged measles infections and with samples from adults who received a trivalent inactivated flu vaccine.
Along with "incomplete reconstitution" of naïve B cells post-measles infection, for example, the team tracked down a measles-related dip in B cell clones that previously expanded to deal with past immune challenges — features that offer a window into the diminished "immune memory" previously described in measles survivors.
"Our results show that [measles virus] infection causes changes in naïve and memory B lymphocyte diversity that persist after the resolution of clinical disease," the authors wrote, "and thus contribute to compromised immunity to previous infections or vaccinations."
Similarly, the team saw decreased antibody levels and poorer B memory immune cell responses to the influenza H1N1 virus in flu vaccinated ferrets that had been through a measles-like canine distemper virus infection than in the animals that remained canine distemper virus-free.
"[T]he 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," co-senior author Paul Kellam, an infectious diseases researchers affiliated with the Imperial College London and the UK-based biotech company Kymab, said in a statement. "This shows that measles could reverse the effects of vaccination against other infectious diseases."