by Renée de Pooter, PhD
Staff scientist in the Department of Pathology
Every year as the days get shorter and kids head back to school, we are reminded of both the vulnerability and the importance of our immune systems. Your doctor, your family and friends, maybe even your employer asks if you’ve had your flu shot yet.
It’s an important question. The CDC estimates that the 2015-2016 flu season cost the US economy $7 billion in lost productivity and contributed to 12,000 deaths. And those who have survived the flu aren’t likely to forget the cough, high fever, muscle pain and sheer debilitating exhaustion.
Every year, vaccine manufacturers churn out 179 million doses of vaccine, an estimated $1.6 billion/year industry. That’s a lot of money for something that does not always work well.
Every year, flu vaccine manufacturers have to make an educated guess about which strains of flu to include in their vaccine, based on the recommendations of the World Health Organization. In the northern hemisphere, the guessing game starts in spring, to assure there are stockpiles of that year’s vaccine ready before the December-to-March flu season.
There is no sure way to predict how the flu will mutate from year to year. Like an errant monk distracted by worldly thoughts, the flu virus is a poor copyist: every time it replicates it makes little mistakes that cause small changes, called “antigenic drift.” More dramatically, because some types of flu can infect pigs or fowl as well as humans, these animals can pick up a completely different version of a gene from another virus that infects the same animal. Those viruses can undergo an even more profound “antigenic shift,” as if the befuddled monk started one day by copying from an entirely different book.
The 2015-2016 flu vaccine was pretty successful, with an estimated vaccine effectiveness (VE) of 48 percent. The 2014-2015 vaccine was less effective and had an overall VE of just 19 percent. More worryingly, it’s hard to predict real wild-card events, like the antigenic shift that created the 1918 pandemic.
By tapping into our immune system’s memories, Patrick Wilson, PhD, associate professor of medicine at the University of Chicago, hopes his research will lead to a universal flu vaccine, one that will protect everyone, perhaps for a lifetime.
The best vaccine targets are the proteins that stud the outside of the virus particle like sprinkles on a cupcake. If the vaccine can goad the body into making antibodies that lock onto the sprinkles, the virus can’t infect human cells. Over time, scientists have learned that the most protective antibodies tend to focus on a protein called hemagglutinin.
Hemagglutinin is shaped like a lollipop, a slender stalk with a big blob—the head region—at the end. While the stalks of different flu strains are pretty similar, the head regions are highly mutable, changing every year. Unfortunately, immune-soldier cells—the B cells—tend to get fixated on the sugary ball of the lollipop and ignore the blander stalk. In doing so, they miss the chance to create an immune memory that would offer broad protection against multiple strains of flu.
Viruses have evolved to use this sneaky distraction technique to elude the host’s immune system.
To better understand how vaccines and the flu shape our immune system, Wilson and his group looked at individual B cells in people vaccinated against the flu. They found that the B cells that produced antibodies against the stalk were hold-overs from previous immunizations/infections, multiple-tour soldiers called memory B cells. They went on to prove that the antibodies made by these stalk-specific memory B cells could protect people against new strains of flu they’d never encountered, confirming that immunity to the stalk confers broad protection against the flu.
Wilson’s group is now working to better understand which vaccination strategy would get the body’s B cells to ignore the tempting head region and make more antibodies against the stalk. If they can figure this out, we could design vaccines that protect against the flu year after year, saving thousands of lives and billions of dollars.
Read about how evolution helps to forecast the flu in the University of Chicago Medicine’s ScienceLife.
