What was your first flu?

Were you born in an H1N1 year or an H3N2 year? The first type of influenza virus we are exposed to in early childhood dictates our ability to fight the flu for the rest of our lives, according to a new study by Canadian researchers in demography and immunology.

Published this week in the journal Clinical Infectious Diseases, the findings by scientists at Université de Montréal and McMaster University provide compelling new evidence to support what's known as ‘antigenic imprinting’.

According to that hypothesis, early exposure to one of the two flu strains that circulate every year imprints itself on our immunity and disproportionately affects the body’s lifelong response to the flu.

This could have important implications for pandemic and epidemic planning, allowing public health officials to assess who might be at greater risk in any given year, based on their age and what viruses were dominant at the time of their birth.  

“We already knew from our previous studies that susceptibility to specific influenza subtypes could be associated with year of birth," said lead author Alain Gagnon, a demography professor at UdeM. "This new study goes much further in support of antigenic imprinting."

A unique 'natural experiment'

Working with his graduate student Enrique Acosta, Gagnon went further than just confirming that specific age patterns are associated with one subtype or the other during a single influenza season.

"We took advantage of a unique ‘natural experiment’ – with observational data – to show how the change in subtype dominance during one season appears to lead, practically in real time, to a change in susceptibility by age," Gagnon said.

The researchers analyzed weekly sentinel data from the Institut national de santé publique du Québec (INSPQ) from the 2018-19 flu season, which was highly unusual because both strains of influenza A dominated at different periods of time.  Typically, only one strain dominates each flu season and accounts for almost all cases.

The scientists found that people who were born when H1N1 was dominant have a much lower susceptibility to influenza during seasons dominated by that virus than during seasons dominated by H3N2. In turn, those born in a H3N2 year are less vulnerable to influenza A during seasons dominated by H3N2.

For instance, older adults who were exposed at younger ages to the H1N1 virus, which emerged during the Spanish flu pandemic in 1918, have many antibodies to fight the virus and therefore do quite well when exposed today to the 2009 H1N1 virus, a close cousin. But in a H3N2-dominated season, they do poorly, with significantly higher mortality rates.

On the other hand, people born during the 1968 pandemic caused by H3N2 are better equipped to deal with influenza during seasons when H3N2 is dominant. In 2017-18, for example, there was a small dip in the incidence of influenza of people born between 1968 and 1977.

12,200 hospitalizations, 3,500 deaths

Health Canada estimates that influenza causes approximately 12,200 hospitalizations and 3,500 deaths every year.

"People’s prior immunity to viruses like flu, including the current coronavirus, can have a tremendous impact on their risk of becoming ill during subsequent epidemics and pandemics," noted the study's co-author, immunologist Matthew Miller, an associate professor at McMaster.

“Understanding how their prior immunity either leaves them protected or susceptible is really important for helping us to identify the populations who are most at risk during seasonal epidemics and new outbreaks,” said Miller.

The researchers hope to further explore transmission dynamics by analyzing how viruses spread within households, where exposure is high and prolonged.  In this environment, they can assess how imprinting may or may not affect the transmission of each strain.