Shots fired? Researchers kill flu virus without a vaccine

Researchers from Ohio State University have reportedly discovered a new way to help a person’s body combat the flu virus, boosting immune response without the need for a vaccine based either on the pathogen itself or the powerful infection fighting substance interferon.
Writing in the latest edition of the journal PLOS Pathogens, the study authors reported that their technique involves increasing the level of a protein known to be effective against every strain of influenza tested to date. To do so, however, they needed to boost the levels of this protein before the virus entered a person’s system, and they did this by manipulating a specific enzyme.
The flu-fighting protein is known as for interferon-induced transmembrane protein 3 (IFITM3), and under natural conditions, it’s only mass produced once the flu virus is present in a person’s body. It combats the pathogen by disabling its ability to make copies of itself, the research team explained, and increasing its levels prior to infection could prevent it from occurring.
Allowing the body to accumulate flu-fighting proteins
If the immune system believes IFITM3 is not actively needed to combat influenza, enzymes known as NEDD4 are released. These enzymes degrade the IFITM3 protein, attaching a small chain of molecules to it (a process called ubiquitination), and in a series of experiments, the authors were able to inhibit its function and allow the flu-fighting protein to accumulate.
“In our work so far, we’ve used genetic techniques to either knock out or silence the NEDD4 gene,” senior author Jacob Yount, an assistant professor of microbial infection and immunity at OSU, explained to redOrbit via email. “In mouse cells genetically engineered to lack NEDD4, IFITM3 levels go up dramatically and the cells become much more resistant to infection.”
“We then used a genetic tool called siRNA to shut down the production of NEDD4 in human lung cells. Again, depleting the cells of NEDD4 caused IFITM3 to accumulate which made the cells resistant to infection,” Yount added. “When we eliminate NEDD4 from cells, this allows IFITM3 to accumulate to high levels that are necessary for its full effect on influenza virus.”
“We’ve known for several years that high levels of IFITM3 can very effectively inhibit flu infections,” he concluded. “The body naturally increases IFITM3 levels when it senses that a flu infection is present so that the spread of the virus can be limited. What we’ve identified is a new molecule, namely NEDD4, that can be targeted to increase IFITM3 levels prior to infection.”
Flu shots aren’t going away anytime soon, though
While the findings are promising thus far, Yount and his colleagues caution that this treatment is still many years away from potentially being used in humans. Their new study involves mice and cultured cells to test experimental drugs exploiting this flu prevention technique under laboratory conditions. Their ultimate goal, however, is to do away with the need for flu vaccines.
“Our research in this publication was done on cells in culture. 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 lungs,” he said. “We are now developing and testing specific drugs that inactivate NEDD4. The first stage of this work is to examine the safety and efficacy of these drugs in mice.”
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