Duke researchers make significant progress in search for more effective, longer lasting flu vaccine

On the heels of a state-wide flu outbreak, a team of Duke and Harvard researchers are making promising developments in the search for a longer-lasting and more versatile influenza vaccine. 

A December study published in The Proceedings of the National Academy of Sciences highlighted the researchers’ newest discovery: a site, or epitope, on the influenza virus molecule that could potentially allow scientists to target multiple strains of influenza with the same antibodies. 

“The problem is that the [current] vaccines aren’t particularly good,” said Garnett Kelsoe, James B. Duke distinguished professor of immunology at the School of Medicine and researcher on the project. “In fact, on average, their efficacy measured as protection against disease, not just infection, … is only about 50% over a 20-year average in Europe and the United States.” 

This inefficacy is largely due to the emergence of new strains each season, created by evolutionary pressures on the virus to mutate. Scientists participate in annual guesswork to predict the next dominant variant. Occasionally, Kelsoe said, they guess incorrectly.

“You have to update the vaccine every few years and try to come up with a better match for future strains,” said Michael Moody, professor of pediatrics and immunology at the School of Medicine. “... [The] flu is going to diversify. We can try to deal with that diversity, or we can try to look at areas of the virus that are relatively constant and try to attack those.” 

Kelsoe and his team began their search in hopes of producing a vaccine that would have longer-lasting effects against a larger variety of influenza strains, reducing the need for a yearly shot. They searched for virus structures that are present in all flu viruses, instead of specific strains, as well as virus sites that cannot be easily changed.  

The newly discovered epitope is present in over 90% of all known virus molecules, making it an ideal candidate for vaccine targeting. 

If developed, a vaccine designed to detect this epitope in different flu variants could provide widespread protection and alleviate the scientific community of the uncertainty involved in predicting the newest strain.

Moody is more unsure. 

“I don’t know if getting a better vaccine will actually increase acceptance rates,” he said. “... There is a tremendous mistrust of experts now.” 

For Moody, the overarching goal is simple: to improve communication with the public about vaccines. 

So far, the research has only been tested in mice. After being infected with 10 to 20 times the ‘lethal’ dose of influenza virus, the mice who were introduced to the epitope-targeting antibodies survived with little to no change in weight. Those who were not part of the treatment group experienced significant weight loss, a key indicator of illness, and eventually died.

The changes seem promising. Kelsoe hopes that a vaccine could be produced as soon as 3 to 4 years from now. “We know that the epitope is highly immunogenic — it would be a good vaccine candidate.” 

Moody asserted the importance of bringing the research to trials in primates, noting that sometimes “mice lie.”

“Of course, what we all want is a one-shot vaccine that will protect you for the rest of your life against all flu strains and has no side effects,” he said. “But that’s not how the real world works, so we’re trying to use the tools we have to solve these problems.”