Your birth year predicts\u2014to a certain extent\u2014how likely you are to get seriously ill or die in an outbreak of an animal-origin influenza virus, new research suggests.<\/span><\/p>\n Until now, scientists thought that previous exposure to a flu virus conferred little or no immunological protection against new influenza viruses that can jump from animals into humans. The new results, published in Science, could hold important clues for public health measures aimed at curbing the risks of a major flu outbreak.<\/span><\/p>\n \u201cEven a comparatively weak, mild pandemic flu event like the 2009 H1N1 (swine flu) outbreak is a trillion-dollar affair,\u201d says Michael Worobey, head of the University of Arizona\u2019s ecology and evolutionary biology department and one of the two senior authors of the study. \u201cA major pandemic like the one we saw in 1918 has the potential to kill large numbers of people and shut down the world\u2019s economy.\u201d<\/span><\/p>\n The research team studied two avian-origin influenza A (\u201cbird flu\u201d) 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.<\/span><\/p>\n First exposure as a child<\/span><\/p>\n 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.<\/span><\/p>\n This effect of \u201cimmunological imprinting\u201d appears to be exclusively dependent on the very first exposure to flu virus encountered in life\u2014and difficult to reverse.<\/span><\/p>\n 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 \u201cflavor\u201d groups.<\/span><\/p>\n \u201cIn this analogy, let\u2019s say you were first exposed to a human \u2018orange lollipop\u2019 flu as a kid,\u201d Worobey says. \u201cIf later in life you encounter another subtype of flu virus, one from a bird and one that your immune system has never seen before but whose proteins also are of a similar \u2018orange\u2019 flavor, your chances of dying are quite low because of cross-protection.<\/span><\/p>\n \u201cBut if you were first infected with a virus from the \u2018blue lollipop\u2019 group as kid, that won\u2019t protect you against this novel, \u2018orange\u2019 strain.\u201d<\/span> The results provide a functional explanation for a pattern that had vexed epidemiologists for a long time: Why are certain age groups more likely than others to suffer serious or even fatal complications from an infection with novel influenza strains?<\/span><\/p>\n \u201cAll sorts of possibilities have been put forth,\u201d Worobey says, \u201cand here my colleagues from UCLA and I present a strong result showing that whatever other minor factors are at play, there is one really major one, and that is\u2014surprise, surprise\u2014we\u2019re not a completely blank slate when it comes to how susceptible we are to these emerging flu viruses.<\/span><\/p>\n \u201cEven if we\u2019ve never been exposed to H5 or H7 viruses, we have some kick-ass protection against one or the other.\u201d<\/span><\/p>\n All 18 subtypes of influenza A virus hemagglutinin circulate in non-human hosts, primarily birds. But only three\u2014H1, H2, and H3\u2014have circulated in humans over the last century. Until now, there has been no way to predict which of the 18 subtypes might cause the next flu pandemic by successfully jumping from animals, and which age groups would be most at risk if this happened.<\/span><\/p>\n 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.<\/span><\/p>\n In the lollipop analogy, people born before the late 1960s were exposed to \u201cblue lollipop\u201d influenza as children (H1 or H2). The researchers found that these older groups rarely succumb to avian H5N1\u2014which shares a \u201cblue\u201d hemagglutinin\u2014but often die from \u201corange\u201d H7N9. People born after the late 1960s and exposed to \u201corange lollipop\u201d influenza as children (H3) show the mirror-image pattern: They are protected from H7N9 but suffer severe disease and death when exposed to H5 viruses mismatched to their childhood exposure.<\/span><\/p>\n Based on previous work, Worobey thinks that a similar process may explain the unusual mortality patterns caused by the 1918 flu pandemic, which was more deadly among young adults.<\/span><\/p>\n \u201cWhen I was finishing up that work and looking at the age patterns, I noticed something interesting,\u201d he says. \u201cThose young adults were killed by an H1 virus, and from blood analyzed many decades later there is a pretty strong indication that those individuals had been exposed to a mismatched H3 as children and were therefore not protected against H1.<\/span><\/p>\n \u201cThe fact that we are seeing exactly the same pattern with current H5N1 and H7N9 cases suggests that the same fundamental processes may govern both the historic 1918 pandemic and today\u2019s contenders for the next big flu pandemic.\u201d<\/span> In their latest paper, Worobey and coauthors not only 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.<\/span><\/p>\n \u201cIf either of these viruses were to successfully jump from birds into humans, we now know something about the age groups that they would be hit the hardest,\u201d Worobey says, adding that efforts to develop a universal flu vaccine hinge on such insights because \u201csuch a vaccine would likely target the same conserved protein motifs on the virus surface that underlie this age-specific pattern.\u201d<\/span><\/p>\n Based on these findings, Worobey says future research should try to elucidate the exact mechanism underlying the immunological imprinting and finding out possible ways to modify it with a vaccine.<\/span><\/p>\n \u201cIn a way it\u2019s a good-news, bad-news story,\u201d he says. \u201cIt\u2019s good news in the sense that we can now see the factor that really explains a big part of the story: Your first infection sets you up for either success or failure in a huge way, even against \u2018novel\u2019 flu strains.<\/span><\/p>\n \u201cThe bad news is the very same imprinting that provides such great protection may be difficult to alter with vaccines: A good universal vaccine should provide protection where you lack it most, but the epidemiological data suggest we may be locked into strong protection against just half of the family tree of flu strains.\u201d<\/span><\/p>\n Source:\u00a0http:\/\/www.futurity.org\/flu-pandemic-age-1296062-2\/<\/span><\/p>\n
\nWhy some age groups get really sick<\/span><\/p>\n
\nWhat this means for vaccines<\/span><\/p>\n