Flu shot ‘back-boost’ discovery may change the way vaccines are made

This "antibody landscape" allowed scientists to visualize the way a person's immune system responded after being exposed to the flu.
This “antibody landscape” allowed scientists to visualize the way a person’s immune system responded after being exposed to the flu.
(Center for Pathogen Evolution, University of Cambridge)

Did you get your flu shot? If so, you probably figured it would protect you against exposure to the three strains of influenza virus were deemed most likely to circulate this winter. But a new study in the journal Science reveals that the shot primed your immune system to defeat a much broader range of flu viruses, and it suggests a simple tweak to make it work even better.

Every year, 5% to 10% of adults and 20% to 30% of kids around the world become sick with the flu, according to the World Health Organization. For most people, that means a week or two of fever, cough, runny nose, headache and pain in the muscles and joints. But in 3 million to 5 million cases, the flu can cause more severe illness, including 250,000 to 500,000 deaths.

That’s why virologists put so much effort into developing the flu vaccine. It contains samples of weakened or deactivated viruses, enough to make the immune system swing into action and create antibodies. That way, if you encounter a real flu virus, your body will be prepared to fight it.

But influenza is a wily virus. There are three main types – A, B and C – and hundreds of subtypes. And these strains are constantly changing. Experts at public health agencies such as the WHO and the U.S. Centers for Disease Control and Prevention track the ones circulating in people and make their best guess about the three or four versions that are most likely to cause infection and put those strains in the flu shot (or flu mist). The better the match, the more protection, and vice versa.


“During years when the flu vaccine is not well matched to circulating viruses, it’s possible that no benefit from flu vaccination may be observed,” the CDC says.

But the new study in Science challenges that view.

An international research team found that the flu shot prompts the body to make antibodies against all of the flu viruses a person has encountered over his or her lifetime, not just the ones in the vaccine. In fact, the immune response “tends to be highest against strains encountered earlier in life,” they wrote.

The researchers came up with a name for this phenomenon: a “back-boost.”


Their first sign of its existence came from studying the blood samples of 69 people in Vietnam who were born between 1917 and 2005 and tracked for another study. All of them had given blood samples each year between 2007 and 2012. None had gotten flu shots, but they had been exposed to the flu (and sometimes got sick).

The researchers used the blood samples to create 3D computer models that they called “antibody landscapes.” These maps depicted the relationships among various flu strains, along with the strength of the antibody response to each one.

What these landscapes showed was that the strongest immune response was usually to flu viruses that were circulating when people were about 6 years old. Generally speaking, the older the virus, the bigger the response.

“Antibody levels against newly circulating viruses tended to be lower than those against strains circulating earlier in an individual’s lifetime,” the researchers wrote.


They called out the example of a study participant who was born in 1970 and got the flu in 2009. That infection caused the person’s immune system to make antibodies to versions of the 1968 Hong Kong flu strain, which had circulated in the subject’s youth but not in recent decades.

To check whether flu shots prompt this type of back-boost, the researchers piggybacked on two other studies. In both cases, volunteers gave blood samples, got a flu shot, and then gave another blood sample four weeks later.

In one of the studies, the vaccine protected against so-called Wuhan 1995 strains that had already been circulating for a few years. In the other study, the shot was built around a new flu strain that most people hadn’t encountered. However, the researchers discovered that this forward-looking vaccine prompted a “slightly larger” antibody response to Wuhan 1995 viruses than did the vaccine that targeted them directly.

The researchers couldn’t explain the biology behind this back-boost (though they described some of their theories in the study). However, they were pretty clear on the upshot of their finding: When designing a flu shot, you’re better off including new strains instead of old ones. Either way, you get protection against older flu strains. And if you guess right, you’ll get protection for new ones as well.


For a shot of science, follow me on Twitter @LATkarenkaplan and “like” Los Angeles Times Science & Health on Facebook.