Researchers have developed a new type of flu treatment that could have a dramatic impact on the fight against influenza and potentially, other viruses too. This method involves an antibody cocktail, and when it was tested in a mouse model of weakened immunity, it shielded the animals from almost every strain of flu they were exposed to, even potential pandemic viruses like avian or swine influenza variants. The findings have been reported in Science Advances.
Unlike antiviral drugs that target viral enzymes, which can evolve and evade the impacts of those drugs, this approach involves antibodies, and the treatment did not trigger immune evasion even after repeated exposure in animals over weeks.
The investigators are hopeful that this treatment could be a vital tool in potential outbreaks of flu that can occur in the future.
“This is the first time we’ve seen such broad and lasting protection against flu in a living system,” noted senior study author Silke Paust, an immunologist at The Jackson Laboratory (JAX). “Even when we gave the therapy days after infection most of the treated mice survived.”
It’s been thought that antibodies must neutralize viruses to be effective; in other words, they have to stop a virus from binding to cell receptors and infecting those cells. But this approach involves non-neutralizing antibodies. Instead, the researchers tagged infected cells in the lung to help the immune system target and eliminate those cells, ultimately clearing infections.
This method may, therefore, also change how other drugs are designed to target viral infections for elimination.
“The majority of antibodies our bodies make are non-neutralizing, but medicine has largely ignored them. We show they can be lifesaving. Even with lethal strains like H5 and H7 avian flu, this therapy saved lives long after infection had taken hold,” Paust explained.
In this study, the scientists focused on a small part of a protein made by the influenza A viral genome, called Matrix Protein 2. The portion that was targeted is highly conserved, which means that it does not evolve very often and is found in many flu variants. This highly conserved portion of Matrix Protein 2 is known as M2e, and it is very important to the viral life cycle. It is found in avian, human, and swine flu variants, among others.
The team found that three antibodies each had antiviral effects, but they worked best in combination. The combinatorial approach is likely to reduce the chance for viruses to evolve to evade these antibodies as well. The antibodies reduced the severity of infection, lowered viral load, and improved survival significantly in both immunocompromised and healthy mice exposed to flu infection.
“We can use very low doses, which is also promising because potential therapies could be cheaper and less likely to produce adverse side effects in people,” Paust said.
More research will be needed to confirm these results in humans, and to bring this treatment to the clinic, but it is a major step forward, and could have wide-ranging impacts. This treatment also presents a potential tool if a flu pandemic develops.
“We need something that is off the shelf when we don’t necessarily have the time to make a new vaccine if we do have an outbreak or pandemic where lethality is high, so this type of therapy could be readily available for anyone in any situation,” Paust said.
The investigators are now developing this antibody approach for clinical trials.
Sources: Jackson Laboratory, Science Advances
