Innovative Antibody Cocktail Could Provide Broad Protection Against Seasonal Flu

Researchers at The Jackson Laboratory have developed a groundbreaking antibody therapy that may revolutionize the fight against influenza. Published in Science Advances, the study reports that a specially designed cocktail of antibodies effectively protected mice—including those with compromised immune systems—from nearly all tested flu strains, including avian and swine variants that could potentially cause pandemics.

Unlike existing FDA-approved flu treatments, which target specific viral enzymes and often lose effectiveness as the virus mutates, this new therapy demonstrated resistance to viral escape even after prolonged exposure. This durability could be crucial during future outbreaks, especially since vaccine development typically takes around six months.

Senior author Silke Paust emphasizes that this is the first instance of achieving broad and lasting protection against influenza in a living system. Remarkably, mice treated with the antibody cocktail survived even when treatment was administered days after infection. The approach challenges the traditional belief that only neutralizing antibodies—that directly block infection—are useful. Instead, the team engineered non-neutralizing antibodies that mark infected cells for immune clearance, resulting in effective viral control without inducing resistance.

The target of this therapy is a conserved region of the influenza A virus known as M2e, part of the Matrix Protein 2, which remains almost unchanged across different flu strains. The study found no mutations in this region after 24 days of treatment, indicating a low likelihood of resistance development. The effectiveness was maximized by combining three antibodies, reducing the chances of the virus evading immune attack.

The treatment proved effective at low doses both before and after infection, significantly decreasing viral load in animal lungs and improving survival rates. Notably, a single dose reduced viral amounts even days after infection with highly lethal H7N9 bird flu, with high survival rates when administered early.

Paust highlights the potential for cost-effective, off-the-shelf therapies that could be rapidly deployed during seasonal outbreaks or pandemics. The team is now working on creating a humanized version of the antibodies for clinical trials, aiming to offer protective and therapeutic options for high-risk groups such as the elderly or immunocompromised individuals.

This promising development suggests a future where broad-spectrum, resistance-proof flu treatments could complement or even replace traditional vaccines, providing immediate availability and robust protection against evolving influenza strains.