Influenza has long cast a long shadow over public health concerns. In recent years, fears over a possible global pandemic of swine or bird flu have thankfully not yet been realised. There is even a sub-genre of literature that deals with the impact of deadly flu pandemics, probably the most famous example being Stephen King’s ‘The Stand’, which details how an artificial flu virus wipes out 99.6 % of the world’s population.
Thus with the notion of a flu pandemic still able to capture the public imagination, new research published by a collaborative team from the University of California, Los Angeles, and the University of Arizona in Tucson has raised interest by suggesting why some flu outbreaks are much more deadly for younger people when usually it is the very old or the very young who are seen to be most at risk from flu.
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 the journal ‘Science’, have thrown this seemingly conventional belief into doubt.
A childhood immunological imprint
The research team 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 have caused global concern because they might at some point gain mutations that would allow them to 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 is first exposed to during childhood determines which avian-origin flu strains they would be protected against in a later infection – in essence, a form of ‘immunological imprinting’.
The first time a person’s immune system encounters a flu virus, it produces antibodies targeting hemagglutinin, a receptor protein that sticks out of the surface of the virus, described by the research team as being like a lollipop. Although there are 18 different types of influenza A, there are only two versions, or ‘flavours’ of hemagglutinin, with the researchers classing them as ‘blue’ or ‘orange’ lollipops.
‘In this analogy, let’s say you were first exposed to a human ‘orange lollipop’ flu as a kid,’ lead researcher Dr Michael Worobey says. ‘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.’
In particular, those born before the late 1960s were exposed to ‘blue lollipop’ flu viruses – H1 or H2 – as children. As a result, in later life, they rarely fell ill from another ‘blue lollipop’ flu – H5N1 bird flu, but they did die from H7N9 ‘orange lollipop’ flu. Those born after 1968 and exposed to ‘orange lollipop’ flu – H3 – have the mirror image pattern.
Informing public health
These findings could be essential in helping public health authorities to effectively plan for and act during any major future flu pandemic. Dr Worobey and his team showed that there is a 75 % protection rate against severe illness and an 80 % protection rate against death if patients had been exposed to a matched virus as children.
This could also help explain why the 1918 ‘Spanish flu’ outbreak was so much more deadly amongst young adults and killed around 50 to 100 million people – blood analysis decades later showed that there was a high possibility that young adults were exposed to the wrong type of flu as children (H3) that gave them no protection against the Spanish flu (H1).
‘If either of these viruses [H5N1 and H7N9] were to successfully jump from birds into humans, we now know something about the age groups that they would be hit the hardest,’ Worobey comments, adding that efforts to develop a universal flu vaccine hinge on such insights because ‘such a vaccine would likely target the same conserved protein motifs on the virus surface that underlie this age-specific pattern.’