To a certain extent your birth year could predict the chances of you getting seriously ill or possibly dying from a future outbreak of an influenza virus of animal-origin, says a new study. The team behind the new research studied two avian-origin influenza A (bird flu) viruses, H5N1 and H7N9, each of which already has caused hundreds of spillover cases of severe illness or death in humans.
Both strains are of global concern because they might at some point gain mutations that allow them not only to readily jump from birds into humans, but also spread rapidly between human hosts. Analyzing data from every known case of severe illness or death from influenza caused by these two strains, the researchers discovered that whichever human influenza strain a person happened to be exposed to during his or her first infection with flu virus as a child determines which novel, avian-origin flu strains they would be protected against in a future infection.
This effect of ‘immunological imprinting’ appears to be exclusively dependent on the very first exposure to flu virus encountered in life — and is difficult to reverse. When an individual gets exposed to flu virus for the first time, the immune system makes antibodies targeting hemagglutinin — a receptor protein shaped like a lollipop that sticks out from the virus surface.
Like lollipops that come in different colors and flavors, influenza viruses differ from each other in the parts that make up their hemagglutinins. But each of the 18 known influenza A virus hemagglutinin subtypes falls into one of just two main ‘flavor’ groups. Continuing with the lollipop analogy, if a person was first exposed to a human 'orange lollipop' flu as a kid, then, if later in life he or she encounters another subtype of flu virus, one from a bird and one that their immune system has never seen before but whose proteins also are of a similar 'orange' flavor, their chances of dying are quite low because of cross-protection. But the person who was first infected with a virus from the 'blue lollipop' group as kid, will not have any protection against the novel 'orange' strain’ of flu virus.
The results provide a functional explanation on why certain age groups are more likely than others to suffer serious or even fatal complications from an infection with novel influenza strains. Until now, there has been no way to predict which of the 18 subtypes of Influenza A might cause the next flu pandemic by successfully jumping from animals, and which age groups would be most at risk if this happened.
The new study provides insights on both counts by revealing that immunological cross-protection appears to exist within each major branch of the evolutionary tree of influenza A. One branch includes human H1 and H2 viruses as well as avian H5, while the other includes human H3 and avian H7. In the lollipop analogy, people born before the late 1960s were exposed to ‘blue lollipop’ influenza as children (H1 or H2).
The researchers found that these older groups rarely succumb to avian H5N1 — which shares a ‘blue’ hemagglutinin — but often die from ‘orange’ H7N9. People born after the late 1960s and exposed to ‘orange lollipop’ influenza as children (H3) show the mirrorimage pattern: They are protected from H7N9 but suffer severe disease and death when exposed to H5 viruses mismatched to their childhood exposure.
Through their study the researchers show that there is a 75 percent protection rate against severe disease and 80 percent protection rate against death if patients had been exposed to a matched virus as children, but also that one can take that information and make predictions about H5N1, H7N9 and other potential causes of future pandemics. The new study could help elucidate the exact mechanism underlying the immunological imprinting and find possible ways to modify it with a vaccine, preferably a universal flu vaccine that would provide protection against the strain that a person lacks.