Each year millions of Americans head to the doctor to get vaccinated for the upcoming flu season, and each year, there’s a new vaccine, reflecting expert guesses about which viruses will circle the globe this time. Finally, researchers have taken a first step toward an entirely new approach, which would eliminate the need to update flu vaccines every year. In fact, by building up cells’ defenses, it could eliminate the need for flu vaccines altogether.
Unlike polio, measles, or tetanus, there’s a dizzying array of influenza viruses, and they can’t all be prevented by the same vaccine. Swine flu, for example, is caused by the H1N1 virus, while bird flu is caused by H5N1. H and N refer to different proteins on the surface of the viruses; they come in 18 and 11 varieties, respectively. In other words, you’d need a whole lot of different vaccines to guard against every virus. Instead, health officials and vaccine manufacturers try to figure out which flu varieties are on their way this year and then prepare vaccines accordingly. But predicting impending outbreaks is a tricky thing, and predictions sometimes fail.
Impeding NEDD4 cut cell-level infection rates below 10 percent.
Graduate students Nicholas Chesarino and Temet McMichael, along with their advisor Jacob Yount, an assistant professor of microbial infection and immunity at the Ohio State University, decided on a new approach: Rather than up the immune system’s offense as a vaccine would, they chose to instead boost cells’ defense—specifically, the antiviral protein IFITM3, which blocks flu viruses from breaking and entering cell walls. Since all influenza viruses enter cells the same way, Yount writes in an email, raising IFITM3 levels should stop all influenza viruses, regardless of type.
Yount explains that, while the body is constantly producing IFITM3, it’s also recycling it into other proteins with a second compound called NEDD4. Chesarino, McMichael, and Yount’s idea, then, was to suppress NEDD4, thus allowing IFITM3 to build up and prevent flu infections before they start. The team tested that idea in human lung cells and in mice by interfering with the production of NEDD4 and then attempting to infect them with two influenza viruses, H1N1 and H3N2. In human cells, impeding NEDD4 cut cell-level infection rates below 10 percent, while in a control group, more than a quarter of human lung cells were invaded by viruses, with similar results in mice.
Still, that doesn’t mean you’re going to see new drugs targeting NEDD4 this autumn. For one, Yount writes, the researchers don’t yet know whether there might be side effects of tinkering with antiviral proteins, and they are also just beginning to look for drugs that could target NEDD4 production. “The challenge of translating this work into humans is that we will need to find ways in which to safely silence or inhibit NEDD4 in the lung,” Yount writes.
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