A universal flu vaccine that would only have to be injected a few times over the course of a lifetime is closer to reality than ever before.
Researchers at the University of Pennsylvania's Perelman School of Medicine announced Wednesday that they were able to protect mice, rabbits, and ferrets from a few flu strains by changing how they attacked a flu virus’ protein structure.
"If it works in humans even half as well as it does in mice, then the sky's the limit—it could be something that everyone uses in the future to protect themselves from the flu," co-senior author Scott Hensley, an associate professor of microbiology, said in a press release about the report published in Nature Communications.
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Penn’s vaccine is the latest in the race to find a universal flu vaccine, one that would not only reduce the physical pain and annoyance of going to a clinic every season to get a flu shot but also works.
The vaccine we're used to is based on researchers’ prediction of what that season’s flu will look like, creating a cocktail of the potential forms of these strains. The idea is fairly simple: Patients get injected with the best-guess vaccine, and within a couple weeks, the body creates antibodies, essentially training the immune system to fight that particular virus off.
The problem, as anyone who suffered through the flu last year might know, is that the protective ability of a given flu vaccine depends entirely on researchers correctly predicting which form will dominate the season. (The efficacy of last year's vaccine was 36 percent, according to a CDC report—not even as bad as the 20 percent efficacy rate of the 2014/2015 flu season.) Then there’s the issue of mutation, which can make a vaccination less effective and knock an infected person for a loop.
That’s what makes a universal flu vaccine such an attractive concept. It would work on all strains, even those that mutate. And that means you wouldn’t need to get a new shot every year.
So what’s the problem? Well, it turns out that making a universal flu vaccine is really difficult.
Normally, the flu vaccine attacks the hemagglutinin (HA) protein, which is shaped like a mushroom with a bulbous top and a thinner "stalk." The head part of the mushroom-like HA helps the virus infect a human cell, Drew Weissman, a senior co-author, told The Daily Beast via email. Antibodies released by the immune system after a flu shot are normally directed towards the "head" of the HA protein. That's problematic, because the head of the HA protein mutates quickly and is the primary reason why strains of flu in one season are completely different the next.
The vaccine the Penn researchers tested on the mice doesn't target the HA protein directly and instead uses mRNA molecules, which convey genetic information to cells. The mRNA cell essentially teams up with the immune system, then gets "translated" into copies of the HA protein during cell production. The resulting proteins do a much better job copying real flu viruses by getting within the cell's actual DNA rather than simply attacking the ever-changing head of the HA protein.
So the team did just that. Mice, rabbits, and ferrets were immunized once or twice with mRNA just below the dermis level of the skin four weeks apart, then exposed to various influenzas after vaccination.
It worked beautifully. Rates varied between strains, but responses were overall much improved over normal flu vaccines. The antibody response was not only strong, it lasted for 30 weeks after the experiment. The most notable result was that the response of the HA protein was stronger than it had been four weeks after immunization. In other words, the HA protein stalk actually became more resilient against infection over time.
"When we first started testing this vaccine, we were blown away by the magnitude of the antibody response," Hensley said in the press release. Even when healthy mice were injected with lethal levels of the three flu strains, it worked and the mice survived.
The researchers might have solved the annoyance factor. The Penn vaccine could be injected into a person a few times over the course of their life, similar to the once-a-decade tetanus vaccine.
The next step involves testing in primates, then humans, and going through the Food and Drug Administration. Weissman said he thinks the results are very promising, particularly because ferrets and rabbits—one step above mice in the vaccine testing model—responded well.
"We hope to be in human phase 1 clinical trials within two years," he said.
That's fast, primarily because using mRNA proteins makes pharmaceutical development less expensive and faster. "Current egg-based flu vaccines take nine months [from prediction to development]," Weissman pointed out. "With mRNA, a new vaccine could be produced in weeks in the event of a new influenza pandemic outbreak."
