Your very first flu infection may impact susceptibility, vaccine effectiveness later on in life

CHICAGO — Influenza viruses are notorious for their ability to rapidly mutate and escape preexisting immunity. This characteristic is thought to be the primary driver behind the high incidence of infection in humans, despite massive vaccination campaigns. With a new flu season always on the horizon, a recent study shows that the first type of flu you come down with may have a lasting impact on susceptibility to influenza infections later on.

Moreover, researchers from the University of Chicago say that early childhood influenza infections may also factor into the effectiveness of seasonal flu vaccinations.

In the U.S. alone, influenza leads to between 100,000 to 600,000 hospitalizations and 5,000 to 27,000 deaths per year. This is true even in previously infected older children and adults. The new study in the journal eLife finds that the identity of the initially-infecting flu strain may give patients some protection against that same strain in future flu seasons.

The many faces of the flu

Using statistical modeling software, researchers from the University of Chicago set out to quantify how human susceptibility to seasonal flu viruses arises and changes over time. Influenza in humans is classified as one of three types: A, B, or C. Influenza A and B cause seasonal epidemics of disease. Type C is less common and causes milder symptoms.

The “A” viruses are further broken down into subtypes according to their surface proteins. These proteins are called hemagglutinin (H) and neuraminidase (N), and they are important for the virus to infect cells. The virus mutates these proteins regularly because they are a main target of the human immune response against flu. H1N1 and H3N2 are influenza A viruses that currently circulate in humans.

While H1N1 disproportionately infects children, H3N2 tends to drive more serious cases in adults. Scientists suspect the differences in age distribution between these two flu strains may be a result of different rates of viral evolution. There have been exceptions to this theory however, as more hospitalizations and deaths were recorded among adults during the 2009 H1N1 epidemic.

“Since the risk of influenza infection in a given age group changes over time, factors other than age may affect our susceptibility to infection,” says lead study author Philip Aravelo in a release. “We wanted to see whether these differences can be explained in part by the protection gained from childhood flu infection, which has lasting impacts on the immune response to future infections and the protection against new influenza A subtypes.”

Protection against future infections

In their study, the authors explore how “original antigenic sin” and “immune imprinting” could explain the differences in the age groups affected by each influenza A subtype over time.

Aravelo and his team use statistical models to measure the effect early exposure to the flu has on vaccine effectiveness. Nearly 4,000 seasonal flu cases in Marshfield, Wisconsin from the 2007-2008 to the 2017-2018 flu seasons are examined in the study. Each case involves a patient diagnosed with influenza in an outpatient setting who was older than six months of age.

The team’s model shows that initial infection with a particular subtype of influenza virus may provide some protection against future infections with the same strain. This effect is stronger with H1N1 than with the H3N2 strain. Researchers believe this could be due to the slower evolution of H1N1, which may grant patients longer lasting protection.

The study also finds vaccine effectiveness varied with both age and birth year, indicating a possible impact of early influenza exposure. The authors note their model could not determine whether vaccine effectiveness was primarily affected by the specific identity of the first influenza virus a patient was exposed to, or whether it was influenced by a series of different strains that patients around the same age would encounter early in life.

Regardless, the variations in effectiveness among similar aged people presents a challenge for future vaccination strategies.

“We hope the findings from our study will improve our understanding of influenza epidemiology and the low and variable effectiveness of the seasonal flu vaccine,” senior study author Sarah Cobey says. “This would lead to better forecasting and vaccination strategies to help combat future flu seasons.”

Update: Another study suggests that  the tetanus vaccine lasts into adulthood.