This year’s deadly flu made the quest for a universal flu shot more urgent

At least 40 different universal flu vaccine candidates are being developed right now, but a flu season without the flu is still a long way away.

The goal is to create a vaccine that can protect people against a broad range of flu viruses for at least a year or longer. Doing this would mean no more guessing about which strains will be circulating the following year. More broadly effective vaccines could make for fewer sick people. Some universal flu shot candidates are already being tested in people, and the companies that figure out how to make a universal flu shot stand to make a lot of money.

They also stand to solve a big public health problem because the flu can be serious, even fatal. This year, the flu sent a record number of people to the hospital and killed at least 114 kids in the US alone. Children, the elderly, the immunocompromised, and even the apparently healthy are all at risk from the seasonal flu viruses we were expecting. If a pandemic virus were to emerge unexpectedly, even more people could die. The 1918 Spanish flu killed 50 million people, for instance. The relatively mild swine flu pandemic in 2009 killed more than 280,000.

This year’s devastating flu season “just underscored the urgency,” says Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, or NIAID. “We need to get away from this issue of each year having to race and chase after what we — hopefully, correctly — predict is going to be the flu that attacks us.”

Unfortunately, we just don’t know which parts of the flu virus to target with a universal vaccine to get broad, long-lasting protection. So last week, Fauci and the NIAID outlined key research questions to answer en route to a universal flu vaccine. That kind of basic science takes money, and in the 2017 fiscal year, the NIAID spent only about $64 million on universal flu vaccine research, Bloomberg reports. (For scale, that’s about two-thirds of a single F-35 fighter jet.)

“I don’t control the money,” Fauci says. “I do the science.” There could be more funding on the way: Sen. Ed Markey (D-MA) recently introduced an act that would boost universal flu vaccine funding by $1 billion over five years, according to Bloomberg. If they get additional money, Fauci says, “that will be money well spent. If we don’t get additional money, I’m still going to prioritize it.”

To understand why developing a universal flu vaccine is so hard, it helps to know a little bit about how the seasonal flu vaccine works. Right now, seasonal flu vaccines target ice cream cone-shaped proteins studding the flu virus’s coat. Most of the immune response is directed against the ice cream scoop at the top of the protein, rather than its cone-like stem. But the flavor of that scoop can change rapidly, so the seasonal flu vaccine needs to be reformulated yearly.

The strategy leaves vaccine manufacturers unprepared and scrambling if an unexpected virus emerges — like the H1N1 swine flu pandemic in 2009, which peaked before vaccines were ready. “You’re trying to predict the future,” says Florian Krammer, a microbiology professor at the Icahn School of Medicine at Mount Sinai. “And every now and then, we get this prediction wrong.”

Right now, the contestant leading the clinical trial race is a UK-based company called Vaccitech. It’s developing a flu shot that prompts a person’s immune system to bring out its big guns, like killer T-cells, rather than antibodies to fight the flu. And it’s currently testing its flu vaccine in people to see if it works. The effort has attracted $27 million in funding from venture capital groups including Alphabet’s GV (formerly Google Ventures), but it will take more to keep going. “The point of this study is to show some preliminary evidence of efficacy so we can raise more money so we can afford to do a phase III trial,” says Vaccitech’s Sarah Gilbert, a professor of vaccinology at the University of Oxford. “We’re years away, but so is everybody else.”

Next up is a Wisconsin-based company called FluGen, which has genetically modified a flu virus that can infect cells, but can’t multiply inside them. That keeps the virus from spreading through the body or to other people. “It’s kind of like a roach motel,” says the company’s executive chairman Boyd Clarke. “It can check in, but it can’t check out.” The theory is that vaccinating with a genetically modified strain of flu virus generates a big enough immune response that it could protect people against other similar strains as well. It’s similar to the FluMist vaccines that use living, but weakened, flu viruses — but it’s more like a wildtype virus, explains FluGen virologist Pamuk Bilsel. The real test is coming this summer: the team plans to test whether vaccinating with a strain of the H3N2 flu virus that circulated in 2007 protects study participants against another H3N2 strain that circulated in 2013.

Then there are the teams still in early safety trials or just about to start them. Two of them are taking aim at the sugar cone part of that surface protein, rather than the rapidly changing ice cream scoop. At Mount Sinai, Krammer and his colleagues are working with pharmaceutical giant GlaxoSmithKline to develop a series of vaccines that pair the same cone with new, exotic flavors. Theoretically, this series of vaccines should teach the immune system to attack the cone, no matter what flavor of ice cream is on top. The vaccines are in early studies in people to make sure it’s safe, and to figure out how the immune system responds to it.

The NIAID’s Vaccine Research Center also has a candidate that should be entering early human trials at the end of 2018. Its strategy is to create a vaccine made out of the ice cream cones, without the ice cream scoop. While the Vaccine Research Center has also partnered with “medium-size biotech and large pharma” companies, it won’t say which ones.

Last but not least is the University of Georgia’s Ted Ross, whose team developed an algorithm that analyzes flu viruses in order to piece together a kind of Franken-protein made out of parts from different strains. This should teach the immune system to fight off a broader range of strains, even if those strains evolve. His team is working with major vaccine manufacturer Sanofi Pasteur, and plans to bring the first of these vaccines to early human trials in 2019, Ross says.

“It’s quite a crowded field already,” Krammer says. But the biggest hurdle isn’t the competition between the teams. “It’s more about getting the funding, and getting the buy-in,” Krammer says. “We’re struggling more with that than with each other.”

Even those companies that make it through the long, expensive process of human testing may not be able to call their vaccines “universal,” says Vaccitech’s Gilbert. That’s because of how the regulatory process works. The first step will be to show that a potential universal vaccine works against seasonal flu. After that comes the process of showing that it works against pandemic viruses. “It’s going to be a long time before there’s a licensed universal flu vaccine,” Gilbert says. “And it’s not going to be cheap to get there.”