A new study may help explain why flu vaccines work so poorly.
It finds that when testing how well an experimental new vaccine works, researchers may be looking in the wrong place — or at least they're not looking in all the places they should.
The study by a team at the National Institute for Allergy and Infectious Diseases (NIAID) found that vaccines work better when they stimulate an immune system response to a flu component called neuraminidase. However, most vaccines target a different protein called hemagglutinin, and most trials of new flu vaccines test how well they work against hemagglutinin.
"This new study provides some interesting clues about how we might improve the level of protection that flu vaccines provide," NIAID Director Dr. Tony Fauci said in a statement.
Flu vaccines aren't the best — many years they barely protect against the most common strains. There are many reasons for this: they're based on very old technology, the flu virus mutates quickly and unpredictably, and different strains of flu circulate and compete constantly.
Some years they protect people well, and other years they don't.
The NIAID team tested 65 healthy people who volunteered to be infected with influenza on purpose.
"The idea behind this study was to re-evaluate the bar that was previously established for evaluating a person's immune response to influenza vaccines," said NIAID'S Dr. Matthew Memoli, who led the study.
"We wanted to test the conventional wisdom and see if people with high levels of hemagglutinin antibodies were less likely to develop mild-to-moderate influenza compared with those with lower hemagglutinin antibody levels."
Hemagglutinin gives influenza A viruses the "H" in their names — H1NI, H3N2, and so on. Neuraminidase is the "N." Both are found on the surface of the virus and are easy for the immune system to see and target.
Most flu vaccines contain a piece of the flu virus and almost all of them aim at hemagglutinin, which helps flu viruses attach to the cells they infect. And so tests of how well flu vaccines work tend to look at how well the vaccine stimulates the body to produce antibodies against hemagglutinin.
The 65 volunteers in the latest study were tested to see what kind of flu immunity they already had. Then they had H1N1 flu sprayed into their noses.
The NIAID team found that people who had a good immune response against hemagglutinin had milder flu symptoms. But people with lots of immunity to hemagglutinin were just as likely to have some symptoms of flu as those with low immunity.
What predicted whether they had escaped any flu symptoms was their pre-existing immunity to neuraminidase, they reported in the journal mBio.
"We demonstrate that although higher (hemagglutinin) titer is predictive of some protection, there is stronger evidence to suggest that neuraminidase inhibition titer is more predictive of protection and reduced disease," they wrote.
The findings don't surprise flu vaccine expert Dr. John Treanor of the University of Rochester Medical Center.
He says different parts of the flu virus mutate at different rates.
"Neuraminidase doesn't seem to change as fast as the hemagglutinin does," he said. That means the body's antibodies against neuraminidase might recognize the "N" in a flu virus better from one year to the next.
"The problem with using neuraminidase in a vaccine is that it's biologically unstable," he added. The process of turning a piece of neuraminidase into a vaccine can break it down so it doesn't work as well.
It's also known that influenza vaccines don't have to stimulate a response to neuraminidase to work.
FluBlok, a newer flu vaccine grown in insect cells, only targets hemagglutinin but protects as well as other vaccines do, Treanor said.
So what's the point of this study?
"Learning more about immunity to flu helps us design better vaccines," Treanor said.
The hope is for a "universal" flu vaccine that protects against a range of strains even if they mutate, or drift, over time.
The study also helps explain why many people still get mild cases of flu even after they've been vaccinated.
This year's flu vaccine is one of the most effective in years, the Centers for Disease Control and Prevention says. People who got the vaccine were 59 percent less likely to get sick with influenza than people who didn't, the CDC said.
The flu vaccines on the market deliver a cocktail to protect against three or four strains of flu. It takes months to make flu vaccines and they have to be formulated freshly every year.
Flu puts hundreds of thousands of people into the hospital every year, and kills anywhere between 3,000 and 49,000 people, including many young, perfectly healthy people. This year so far, 50 children have died from flu, CDC reports.