New antibody cocktail shows promise for treating multiple strains of flu

While vaccines can be very effective for preventing viruses, like the influenza A virus (IAV), they are often strain-specific and prone to viral escape mutations. IAV alone is responsible for around 500,000 deaths worldwide each year. To better serve vulnerable populations and prevent pandemic conditions, scientists have been searching for ways to create better, more universal, mutation-resistant, off-the-shelf IAV therapeutics.

Researchers at the Jackson Laboratory in Farmington, Connecticut might just have the solution. Their research, recently published in Science Advances, focuses on non-neutralizing antibodies, which are proteins produced by the immune system, whereas other current antibody therapies focus on neutralizing antibodies. Vaccines rely on the creation of neutralizing antibodies to prevent infection, but non-neutralizing antibodies work by helping the immune system fight off the infection instead—meaning the non-neutralizing antibody therapy is not a vaccine.

The team evaluated three non-neutralizing antibodies that block an essential proton channel (M2e) of IAV. They tested out different variations of the antibodies (in groups of one, two, or all three) to determine prophylactic and therapeutic efficacy in mouse models using multiple IAV strains—including highly lethal avian flu strains. They found that a combination of all three of the antibodies, administered as a kind of cocktail, was highly effective.

“While low-dose combinations of M2e-mAb pairs failed to protect IAV-challenged mice from lethality completely, a triple cocktail composed of M2e-mAbs with competitive binding sites in the M2-protein’s N-terminal region was universally protective and highly effective at low doses. These results suggest that the protection provided by the triple M2e-mAb cocktail is not due to a dominant effect by one or two of the component antibodies but due to all three M2e-mAb cocktail component antibodies acting in synergy,” the study authors write.

The therapy was even effective when administered in the first several days of infection. They found that 100% of the mice infected with the avian flu strain, H7N9, survived when treated on the day of infection (day 0), the next day (day 1), or day 3 postinfection. 80% of the mice treated on day 2 survived.

Unlike traditional vaccine treatments, the antibody cocktail treatment was resistant to viral mutation in both immunocompetent and immunodeficient mice.

The study authors write, “Together, our results have established the triple M2e-mAb cocktail therapy as robustly effective and viral escape mutant-resistant therapy against IAV, including against one of the most lethal IAV subtypes. Our findings are in stark contrast to previously published M2e-mAbs and FDA-approved M2 inhibitors, which rapidly elicit escape mutants in WT and immunocompromised mice.”

While the therapy is impressively promising, it does still need to be tested in humans. If effective in human trials, the treatment can serve as a new off-the-shelf, broadly effective therapy for seasonal and pandemic influenza, especially when new versions of vaccines are delayed or ineffective.

© 2025 Science X Network