Child’s 1st flu could determine lifelong risk, including to bird flu, study finds

The first strain of flu you were exposed to as a child may determine your level of risk in the event of a deadly pandemic of animal-origin influenza, new research suggests.

The study, published in the journal Science, indicates that a person’s susceptibility to bird flu depends largely on year of birth.

The findings could have major implications for how we understand all strains of influenza and protect ourselves from future outbreaks. 

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Scientists at the University of California, Los Angeles, and the University of Arizona looked at all known human cases of two types of avian influenza — H5N1 and H7N9 — for a total of 1,400 cases.

They were trying to figure out why H5N1 tends to affect children, while H7N9 mostly strikes older adults. 

Both strains are passed animal to human, but have shown a limited ability to spread between people, raising concerns they could one day adapt and trigger a pandemic.

The researchers learned that a person’s risk of becoming very sick or dying from these bird flu strains depends, at least in part, on the type of flu virus they were most likely exposed to in youth. 

The study’s authors call it “childhood imprinting.”

“Your immune system imprints on the first influenza infection you have in such a way that even when you encounter a completely new strain that your immune system has never seen before years and years later, you still have such a hugely strong reaction that’s clinically relevant,” co-author Monique Ambrose, a UCLA graduate student, told CBC News.

The ‘lollipop’ effect 

So why does this happen?

Each influenza virus is covered in tiny proteins called hemagglutinin. When your body gets exposed, it produces antibodies to target those proteins.

Although there are many strains of influenza, they generally fall under two main categories, depending on the type of hemagglutinin present. 

“The first influenza you get when you’re a kid is either going to be in Group 1 or Group 2, and it turns out that your immune system imprints to that first influenza that you get,” Ambrose said. “Your immune system is actually able to recognize, remember and then target.”

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In a University of Arizona press release, senior author Michael Worobey, head of the school’s Department of Ecology and Evolutionary Biology, explains the process with a candy-coated 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’ flavour, 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 kid, that won’t protect you against this novel, ‘orange’ strain.”

A 3D print of influenza virus. The virus surface is covered with proteins called hemagglutinin, shown in bluemand neuraminidase, shown in red, which enable the virus to enter and infect human cells. The type of hemagglutinin in a child’s first flu exposure could impact the strains that child is protected from later in life. (National Institutes of Health )

People born before 1968 were likely first exposed to a blue lollipop virus, H1 or H2, researchers say. When they got older, they were not likely to become ill from H5N1 bird flu, according to the study, but many died from the “orange” H7N9.

People born during and after 1968 had the opposite effect: They were exposed in youth to the orange H3 and became more susceptible to H5N1, their research indictes.

The imprinting gave the patients a 75 per cent protection rate against severe disease and 80 per cent protection rate against death, the study found. 

Implications for fighting outbreaks

This discovery could have implications for how we would fend off an outbreak if an animal-origin influenza virus like the bird flu were ever to adapt and spread between people. 

“If we have an idea of what strains have been circulating in the population and which strains people have imprinted to — which we do — we get an idea of which of those animal influenzas might pose the greatest risk to us,” Ambrose said “So that could really affect our risk assessment for different influenza strains.”

Workers from the Animal Protection Ministry cull chicks to contain an outbreak of H5N1 bird flu at a farm in Modeste, Ivory Coast, in Aug. 14, 2015. If this strain ever jumps to humans and triggers a pandemic, new research suggests it would affect people born in the late 1960s the worst. (Luc Gnago/Reuters)

Also, in the case of a pandemic, it could help health authorities plan strategically in developing and distributing vaccines to target the vulnerable populations.

The next step is to look at whether childhood imprinting affects how our bodies fend off existing influenza strains.

“We don’t know that yet, so that’ll be really interesting to study,” Ambrose said.