The First Flu You Ever Had Is Secretly Shaping How You Respond to Infections

influenza visualization
Naina Nair, a 32-year-old dentist from Bombay, stands in front of her 3-D visualization of the influenza virus at the Glasgow School of Art on September 1, 2017, in Glasgow, Scotland. Jeff J Mitchell/Getty Images

The year you were born might predict how you'll respond to this year's flu—and how well you'd fair in a flu pandemic.

A phenomenon known as imprinting might be responsible for an unusual pattern in the ages of people going to the hospital with the flu. Imprinting in this case refers to how our immune response to the flu is shaped by our medical history.

Specifically, the first flu virus a person catches shapes their immune response to other strains encountered later in life. The strain to which we lose our flu virginity, as it were, affects how we react to all the subsequent strains we meet. "The first strain you meet has a special status," said James O. Lloyd-Smith, a researcher at the University of California, Los Angeles.

Dr. Dan Jernigan, director of the influenza division of the Centers for Disease Control and Prevention's National Center for Immunization and Respiratory Diseases, suggested in late January that imprinting might explain why baby boomers are being particularly hard hit this flu season.

Typically, the hospitalization rate for children under the age of four and adults between 50 and 64 years old are about the same. Not this year. Instead, "baby boomers have higher [hospitalization] rates than their grandchildren right now," Jernigan noted.

Usually the imprinting phenomenon protects us by helping the immune system react more quickly to new virus strains. If the hemagglutinin—a protein on the surface of the virus—is similar to the hemagglutinin encountered in prior strains, then the immune system may produce antibodies to the new virus just upon detecting that protein resemblance.

But the flu changes each year. And one major change in 1968 may help explain why baby boomers are at a disadvantage now.

The problem stems from the strain of flu virus to which those boomers first succumbed. Everyone who is currently at least 50 years old was born before 1968. And the 1968 flu pandemic was the first time in decades that a virus with a particular kind of protein on its surface called H3 spread throughout the United States. That means that anyone who is 50 years of age or older this flu season was born too early to be imprinted with an H3 strain of the virus.

But the H3N2 strain is responsible for many of the flu cases in the United States this year. So the typical boomer immune system is relatively less prepared to fight back than those of younger people, who had a chance of being imprinted with an H3 flu strain.

Hemagglutinin proteins separate into two major groups. One group includes the H1 and H2 and H5 proteins, among others, and the other includes H3 and H7. For many people, H1N1 and H3N2 may sound familiar; these are the strains that are often found in North America.

Scientists have found a clear link between flu susceptibility and bird flu viruses; that connection has been easier to trace because humans aren't regularly exposed to them. In a 2016 paper, Lloyd-Smith and his colleague, University of Arizona researcher Michael Worobey, showed that the type of flu virus to which a person was exposed first influenced his or her immune system's response to these bird flu strains, which often include H5 and H7 proteins.

Teasing out the potential impact of imprinting on seasonal flu, however, can be difficult. Specific data can be difficult to find about the severity of a flu case, the strain of flu involved, and the year the person was born. To parse the connection, Worobey has turned to Arizona health records, which have some information noting both the strain of flu a person was infected with and what year that person was born.

virus model NIH
This 3-D printed model of an influenza virus shows that the virus surface (yellow) is covered with proteins called hemagglutinin (blue) and neuraminidase (red) that enable the virus to enter and infect human cells. National Institutes of Health

But some experts already suspect a link. "If I had to bet, I'd say imprinting is involved during this season," said Scott Hensley, a researcher at the University of Pennsylvania. "But it's just too early to know." (Hensley is actively working on research projects to figure that out.)

This year's flu strain is a nasty one, everyone says. But will that be true for flu seasons to come? Again, the flu of 1968 has something to say about that. Currently H3N2 is dangerous for older people, but it wasn't always so scary. "It actually started back in 1968 being described as usually mild in older people," Worobey noted. Those infections may have been milder because the 50-or-older demographic at that time had been imprinted with an H3 virus that circulated before the 1918 pandemic.

It's tempting to think that birth year alone could help people make health decisions. For example, if H3 viruses are prevalent in a given year, then people over 50 might have even more of a reason to have the flu vaccine.

But it's not that simple. Since 1977, both H3 and H1 viruses have circulated. That means it's anyone's guess which strain a millennial may have been infected with first. Scientists are looking for a way to detect an imprint within a person's immune cells, but currently there's no test to tell which virus a person may have been exposed to first.