An artistic representation of antibodies targeting influenza viruses.
Science Photo Library/Alamy
A new therapeutic approach involving a cocktail of antibodies shows promise in combating seasonal flu and potential pandemic strains. While successful in mouse models, human trials are yet to be conducted.
Conventional flu treatments and vaccines primarily rely on the generation of neutralizing antibodies—proteins that bind to specific virus strains to inhibit their ability to infect cells. While these methods have been effective, they may take considerable time to develop and could lose efficacy due to viral mutations. This necessitates seasonal updates to flu vaccines and drives ongoing research into universal vaccines capable of offering broad protection against multiple flu strains or potentially all viruses.
Dr. Silke Paust from the Jackson Laboratory in Farmington, Connecticut, and her team are investigating a different avenue—non-neutralizing antibodies. These proteins, often overlooked in infectious disease treatment because they don’t prevent infection, may help the immune system eradicate the virus by signaling infected cells for destruction.
“Our goal is not to create a vaccine, but to develop a therapy that can be used either preventatively or after infection to reduce severe complications and mortality,” explains Paust.
The team concentrated on antibodies that target the influenza virus’s M2e protein, vital for its replication and relatively unchanged across various strains.
In a series of experiments, researchers assessed the effectiveness of the antibodies individually and in combinations on flu-infected mice, concluding that a combination of three antibodies yielded the best outcomes.
The cocktail was evaluated against two H1N1 strains, including the one that triggered the 2009 swine flu pandemic, as well as two avian strains: H5N1, affecting wildlife globally, and H7N9, which poses serious risks to humans and animals alike.
Results indicated that the cocktail significantly mitigated disease severity and viral load in the lungs, improving survival rates in both healthy and immunocompromised mice. Remarkably, with H7N9, 100% of mice survived when treated within the first three days post-infection; survival rates dropped to 70% and 60% when treatment commenced on days four and five, respectively.
“This marks the first instance of extensive protection against flu in live animals,” comments Paust. Additionally, the antibodies were effective even when administered prior to infection, indicating their potential as a preventative treatment.
Notably, after 24 days of treatment, there were no signs of viral mutations that could confer resistance to the cocktail. “For the virus to evade this treatment, it must overcome all three antibodies simultaneously, which bind in unique ways,” notes Paust.
Dr. Daniel Davis from Imperial College London remarked, “This serves as a proof of principle for utilizing antibody cocktails as a treatment during flu pandemics, potentially used alongside vaccines. However, it must undergo human trials to validate its efficacy.”
Looking ahead, Paust intends to modify the M2e-targeting antibodies to mimic human proteins. This adaptation would help prevent the immune system from recognizing them as foreign invaders. If successful, subsequent safety and efficacy trials would be conducted.
Paust envisions this cocktail as a readily available treatment for seasonal flu outbreaks, ideal for administration to high-risk patients at the onset of flu season, effectively minimizing their illness severity.
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