Posted on Aug 8, 2018
“By the time she is about three years old, a child has usually endured her first influenza infection. If it’s a nasty bout, her temperature will rise and her muscles will ache. She’s probably young enough that she won’t recall the illness — but her immune system will.”
When the virus enters her body, continues Declan Butler in Nature, its presence prompts a pool of immature, unprogrammed immune cells to start competing to become the flu’s tracker and assassin. The winners — cells that bind most strongly to the virus — store a memory of the pathogen, ready to recognize and attack it the next time it strikes.
An image of the devastating 1918 ‘Spanish Flu’ pandemic.
But influenza is an inveterate shape-shifter. Regions of its outer proteins can mutate as it replicates, allowing it to avoid immune detection. When infections with new flu strains occur later in life, the immune system will mount a response based on that first encounter, reacting strongly to recognized regions of the virus, but not to any that have changed. Immune cells can’t tailor any novel antibodies that could help.
How exactly the immune system ‘imprints’ on its first-encountered strains presents a tantalizing puzzle to flu researchers — and solving it could help to combat the virus and improve vaccines.
Scientists suspect that understanding how imprinting works could help them to predict who will suffer most from seasonal strains and pandemics. Mounting evidence suggests that some people fare worse in deadly flu pandemics because their first childhood exposure was to a different version of the virus. Researchers think that this is why young adults experienced higher mortality than other age groups during the deadly 1918 pandemic, in which an estimated 50 million people died worldwide.
Knowledge of imprinting could help virologists to develop more-effective seasonal vaccines that could counteract circulating strains for several years, and a long-sought universal flu vaccine that could protect people for life against entirely new — and potentially pandemic-provoking — subtypes of flu. Imprinting seems to offer some immunity to flu strains related to the first infection. This broad immunity is often seen as a sign that the immune system could be coaxed into offering wide protection. “It does give us hope that we may be able to elicit a broadly protective immune response,” says Aubree Gordon, an epidemiologist at the University of Michigan in Ann Arbor.
Existing flu vaccines could certainly do with some help. Their effects wear off after a few months, and they aren’t very effective even in that brief window; during the 2017–18 flu season in the United States, people who received the vaccine were only 36% less likely to contract flu than those who weren’t immunized, although vaccination can lessen the severity of symptoms in those who do become ill.
Imprinting might help to explain these shortfalls. But right now, the mechanisms behind this process are poorly understood, says Jennifer Nayak, a paediatric immunologist at the University of Rochester Medical Center in New York. Getting to grips with imprinting will be important to researchers who hope to tailor a universal vaccine to fit people with different past flu exposures, says Scott Hensley, a viral immunologist at the University of Pennsylvania in Philadelphia. “The same vaccine given to different people will likely elicit different immune responses, depending on their history,” he says.
In April, the US National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, called for researchers to pitch projects that would explore the effects of imprinting on immunity, as part of a wider effort to fund research into a universal flu vaccine. The agency plans to spend US$5 million on a large cohort study that will recruit and monitor infants from birth for at least three flu seasons to explore at the molecular level how their immune systems respond to initial exposure and subsequent flu infections and vaccinations. Immunizations are usually recommended for babies over 6 months of age.
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