Vaccine could target 20 influenza viruses in a single shot
For a half-century, scientists have been trying to develop a vaccine that would protect against the most dangerous flu viruses.
Now, researchers at the University of Pennsylvania have a new approach, based on the mRNA technology that proved so effective against COVID-19. Their idea is to target all 20 different types of influenza viruses in a single shot.
Their new vaccine wouldn’t save us from needing an annual flu shot. But if it proves out, it could protect against never-before-seen strains of influenza that could cause a pandemic.
Here’s what a study showed and what such a vaccine could accomplish:
Why has it been so hard to develop a universal flu vaccine?
Annual influenza vaccines protect against four strains of flu, but because the strains circulating in people can change so much, we typically need an entirely new vaccine each year to help prevent serious illness.
Plus, with 20 possible types of flu virus, vaccines that protect against four strains likely offer little protection against a pandemic caused by one of the other 16 influenza types. Flu that circulates in birds, pigs and other animals has the potential to jump into people.
Most previous universal flu vaccine efforts have tried targeting parts of the influenza virus that are present across many strains. Unfortunately, these targets have been hard to reach or didn’t provide the hoped-for effectiveness.
By taking aim at all 20 different types of influenza simultaneously, the scientists behind the new vaccine hope to provide at least some protection against all of the possible lineages.
“We decided to throw the whole kitchen sink into this vaccine,” said Scott Hensley, who led the research, published Thursday in the journal Science.
What does this vaccine do that others haven’t been able to?
Using conventional production methods, it wouldn’t be possible to target the full spectrum of flu viruses. But mRNA vaccines can include at least 20 different antigens for essentially the same cost as a single one, said Hensley, a microbiology professor at Penn’s Perelman School of Medicine.
Researchers were pleasantly surprised that their vaccine could effectively target so many different strains at once – and, at least in animals, generate an immune response against all of them simultaneously.
“To have 20 and have robust immune responses to each was very interesting to me,” said Alyson Kelvin, a virologist at the Vaccine and Infectious Disease Organization at the University of Saskatchewan, who was not involved in the research, but wrote an accompanying column. “It’s something I didn’t think was possible.”
In mice and ferrets, which are used in flu studies because they can catch the same influenza strains we can, the vaccine looked just as safe as the typical flu vaccine.
It’s not yet clear how this vaccine might be used, she said. Potentially, it could be updated every few years as the circulating strains change, or maybe even more than 20 lineages could be included: “I don’t know what the limit is.”
How could this shot help limit a flu pandemic?
Scientists have long worried about a flu virus jumping from animals to people, as happened in 2009 with swine flu and has happened roughly once a decade for the past century.
We’ve been relatively lucky in recent years: Flu deaths in the U.S. ranged from just 5,000 last year to more than 50,000 in both 2014 and 2017. Pandemic flu in 1957 and 1968 more than 100,000 each, and nearly 700,000 Americans died of the 1918 flu.
Scientists want to be prepared in case another strain comes along that is both highly contagious and deadly.
People generally have their best immune memory against the first strains of flu they encounter as children. If H1 influenza is common in their early years, as it has been for more than the past decade, then they will likely avoid severe illness from all H1 strains for the rest of their lives. But they might be more vulnerable to other strains.
“Our childhood infections, our first exposures to influenza virus, are super important for affecting how we respond to other influenza strains later in life,” Hensley said.
That’s why during the H1N1 swine flu pandemic in 2009, older people, who had seen H1 influenza during childhood, were less likely to fall ill than people born after 1968, when that variety had stopped circulating.
“Why be at the mercy of whichever influenza strain we encountered early in life?” Hensley asked. “Instead of just being dependent on chance, let’s make a vaccine that introduces all these antigens at the same time.”
Hensley said he would hope to eventually vaccinate a young child against all 20 different flu variants before age 5, providing them broad immune memory for a lifetime. Vaccinating animals that had already been exposed to influenza also provided broad protection, the study showed.
The immune system is used to handling viral proteins by the dozen during an infection, Hensley said, so such a vaccine should continue be safe.
Theoretically, the same shot could also safely deliver antigens against measles, RSV and coronaviruses.
“That is a longer-term goal to try to figure out what is the maximum number of antigens we can include in these vaccines. Can we have 50 antigens or 100 antigens?” Hensley asked. “These are some of the questions we’re working on in my lab right now.”
What needs to happen before this vaccine could become available?
Researchers are currently testing their experimental vaccine in nonhuman primates, after showing it worked successfully in mice and ferrets. Human trials could start as early as next year.
The first trials would probably target no more than five different types of flu, Hensley said, expanding to more if the technology proves out.
Regulatory authorities have never been faced with such broad-spectrum vaccines before, so they will have to develop a framework for analyzing them, which could slow the development process.
“There may be manufacturing or regulatory challenges for a 20-valent vaccine, but this study shows an important proof-of-concept for multiplexing flu vaccines,” said Dr. Dan Barouch, who directs the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston and was not involved in the work.
It will also be challenging to study a 20-variety vaccine, Kelvin said, because the H4 flu lineage, for example, hasn’t been known to circulate in humans.
“I’m in favor of this type of approach,” she said. “I just want us to be having the right discussions on how to regulate it.”