With cash and a call for new ideas, Bill Gates tries to boost the campaign for a universal flu vaccine

Bill Gates is putting his shoulder into the push to develop a universal flu vaccine.

The billionaire philanthropist and Microsoft co-founder announced Friday that his charity — the Bill and Melinda Gates Foundation — is offering $12 million in seed money to spur innovative thinking on a scientific challenge that has stumped the influenza research community for decades and is considered the holy grail of flu research.

The science Gates is hoping to unleash would revolutionize influenza vaccination and render the virus a much less potent threat, both year to year and during flu pandemics. But the figure on offer is a small fraction of what it is expected to cost to develop a vaccine that would generate long-lasting protection against the wide range of flu viruses.

“We think a universal flu vaccine would not only eliminate the pandemic risk, but would have significant health benefits,” Gates said in an interview with STAT reporters and editors, before announcing the funding at a symposium on epidemics organized by the Massachusetts Medical Society and the New England Journal of Medicine. “It would be a fantastic thing.”

The project is timed to the centenary of the 1918 Spanish flu, the worst pandemic on record. It’s estimated at least 50 million people died in that outbreak. Gates warned that a pandemic of equal severity today would kill 33 million people within the first six months, despite the medical advances of the intervening century.

The foundation intends to fund projects that are “game-changing,” not incremental improvements on existing influenza vaccines.

But successful grant recipients will need to move quickly. The foundation says experimental vaccines developed with its money must be ready to be tested in people in 2021 — which leaves scant time for developing a vaccine, testing it in animals, making human-grade batches, and designing the first human trial.

The money is being offered through one of the foundation’s grand challenges, a tool designed to entice out-of-the-box thinking about persistent problems. Google co-founder Larry Page and his wife, Lucy, are also contributing funds.

Individual grants in the pilot phase will range between $250,000 and $2 million, paid out over two years. If a project generates promising proof-of-concept data in animal studies, the scientists involved may be able to apply for an additional $10 million grant later. But that is not part of this funding round.

“This is the early-stage money,” Gates said. “This $12 million isn’t the end of the game.”

There is a rule of thumb that developing a new vaccine costs roughly $1 billion. But the complexity of trying to develop a vaccine to ward off multiple fast-evolving flu viruses suggests that estimate may be low for a universal flu vaccine.

There has recently been renewed interest in a universal flu vaccine, with several senators introducing legislation that would provide $1 billion over five years for the work. For now, the prospects of that bill passing appear slight.

This Gates initiative is aimed at spurring development of a truly universal influenza vaccine — something the director of the National Institute of Allergy and Infectious Diseases, Dr. Anthony Fauci, told STAT earlier this year he thought might be unattainable. Fauci did say, however, that he believes vaccines that protect against seasonal strains, regardless of how they mutate, plus some of the most threatening animal strains, would be a realistic goal.

His agency published a strategic plan for the development of that type vaccine advance in late February.

Asked about Fauci’s statement that a universal flu vaccine was unattainable, Gates paused for several moments, then added: “He’s very good about not overpromising.’’

Though it might seem self-evident that a universal flu vaccine would protect against all types of flu, in reality the term has been appropriated by some to describe next-generation vaccines — vaccines that would protect against a number of flu strains, even when those viruses acquire the types of mutations that foil our current flu vaccines.

The criteria for these awards makes clear those types of proposals will not be considered. But one vaccine to protect against all flu strains is a very tall order.

The viruses that cause the most illness in people are influenza A and B viruses. There are two types of B viruses and two strains of A viruses that sicken people every winter — H3N2, which was the culprit in this year’s severe flu epidemic, and H1N1.

But there are at least 18 hemagglutinins — the surface protein that gives influenza A viruses their H number — and 11 neuraminidases, the N component. That means there are 198 possible combinations, though in reality, some have never been seen in nature.

Despite the scope of the challenge, the mere fact that one of the world’s most prolific philanthropists is interested in helping to fund the quest could draw new minds to this work.

Indeed, the call for proposals explicitly urges applicants to team with scientists from fields such as artificial intelligence, machine learning, and bioinformatics. It also stresses the desirability of drawing in people “new to the influenza field.”

“We’ll see what comes out of the woodwork,” Gates said. “Sometimes we’re disappointed.

“We do these calls for applications many, many times a year, sometimes under the Grand Challenges format, sometimes just a disease-specific thing. And sometimes you don’t get many applications, sometimes you get a huge number.”

In his speech, Gates stressed the need to prepare more for disease outbreaks and potential bioterror events — a departure for the self-proclaimed optimist who likes to focus on the global health gains more than the problems that haven’t yet been solved.

“Not much is being done about the pandemic risk,” he explained in the interview before the speech. “Mostly I share the good news about all the great progress we’re making in global health and people are cheerful after they leave my speeches. This one isn’t likely to do the same thing.

“If some guy’s smiling at the end, watch out for that guy.”