The Connection Between Birth Year and Flu Risk

By Kevin Ritchart

A study led by researchers from both the University of Arizona and UCLA has found a link between the year of a person’s birth and their potential susceptibility to various strains of animal-origin influenza.

Until recently, scientists believed that previous exposure to a flu virus provided little or no protection against new flu viruses that have the ability to spread from animals to humans. But the results of a recent study, which was published in the November 11 issue of Science, could be the key to developing public health measures that could minimize the risk of major flu outbreaks in the years to come.

“Even a comparatively weak, mild pandemic flu event like the 2009 H1N1 (swine flu) outbreak is a trillion-dollar affair,” said Michael Worobey, head of the University of Arizona Department of Ecology and Evolutionary Biology and one of two senior authors of the study. “A major pandemic like the one we saw in 1918 has the potential to kill large numbers of people and shut down the world’s economy.”

The combined research team studied influenza A (also known as bird flu) viruses. The avian viruses known as H5N1 and H7N9 have already caused hundreds of cases of severe illness or death in humans, and both strains are of great concern globally because of the potential for mutation. These mutations could allow the viruses to not only jump from birds to humans, but also possess the ability to spread from one human host to another at a rapid rate.

After combing through data from every severe illness or death caused by both strains of the bird flu virus, researchers found that the human influenza virus a person was exposed to as a child was linked to the strain of avian-origin flu strain they would be protected from in the future. This so-called immunological imprinting appears to scientists to apply only to a person’s first exposure to the human flu virus and may not be reversible. 

What Flavor is Your Flu?
When a person is exposed to the flu virus for the first time, their immune system produces antibodies that target hemagglutinin, a receptor protein that sticks out from the surface of the virus. The makeup of the hemagglutinins in each strain of the influenza virus is different, but in each of the 18 known influenza A viruses, the hemagglutinin subtypes can be split into two main groups. The Arizona and UCLA researchers used the analogy of lollipop flavors to illustrate the differences between the subtypes.

“In this analogy, let’s say you were first exposed to a human ‘orange lollipop’ flu as a kid,” Worobey said. “If 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 ‘orange’ flavor, your chances of dying are quite low because of cross-protection. But if you were first infected with a virus from the ‘blue lollipop’ group as a kid, that won’t protect you against this novel ‘orange’ strain.”

The results of this study answered a question that had been eluding epidemiologists for a long time: Why are certain age groups more susceptible than others to suffer serious or even fatal complications from an infection with novel influenza strains?

“All sorts of possibilities have been put forth,” Worobey said, “and 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 — surprise, surprise— we’re not a completely blank slate when it comes to how susceptible we are to these emerging fl u viruses. Even if we’ve never been exposed to H5 or H7 viruses, we have some protection against one or the other.”

Of the 18 subtypes of influenza A hemagglutinin that come from non-human hosts (primarily birds), only three — H1, H2 and H3 — have circulated in humans in the past 100 years. Until now, there has not been a reliable way to predict which of the 18 subtypes might be responsible for causing the next fl u pandemic by jumping from animals to humans. There also has been no way to definitively identify which age groups would be most at risk.

Increasing Protection
This new study has revealed that immunological cross- protection appears to exist within every major strain of influenza A. One branch in the evolutionary tree of the influenza A virus contains human H1 and H2 as well as avian H5, while the other includes human H3 and avian H7.

In the lollipop analogy, those born before the late 1960s had exposure to “blue lollipop” influenza (H1 or H2) during their childhood. Researchers found that these older groups rarely succumb to avian H5N1 — which contains a shared “blue” hemagglutinin — but often die from the “orange” H7N9. People who were born after the late 1960s and were exposed to “orange lollipop” influenza (H3) as children have shown the opposite effect: They are protected from H7N9 but are susceptible to severe disease and death when exposed to H5 viruses that don’t match their childhood exposure.

Based on recent findings, the next step for researchers will be to further identify the root causes for immunological imprinting and find ways to modify vaccines to account for the varying needs of patients of all ages. “In a way it’s a good-news, bad-news story,” he said. “It’s 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 ‘novel’ flu strains. The bad news is the very same imprinting that provides such great protection may be diffi cult 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.”