Antibody treatment prevents severe bird flu in monkeys

The broadly neutralizing antibody, which recognizes a relatively stable region of the bird flu virus, is less prone to losing its efficacy than antibodies targeting influenza's more mutation-prone structures. This feature ensures that the immune protection can withstand the possible emergence of virus variants, akin to the SARS-CoV-2 mutants that evolved during the COVID-19 pandemic, and provide lasting protection against a globally spreading airborne infection.

"This type of prevention can be very useful in controlling infection outbreaks and containing the bird flu pandemic," said co-corresponding author Douglas Reed, Ph.D., associate professor of immunology at Pitt's School of Medicine and the Center for Vaccine Research. "In our testing, the antibody performed beautifully. The antibody could be useful as a prophylactic of severe disease in vulnerable populations, and it also helped us establish the testing threshold for antibody levels in blood, which would be useful for judging the immune protection generated by a universal flu vaccine."

While, as of January 2025, only one reported case of H5N1 infection in the U.S has resulted in death, the World Health Organization has reported over 950 cases globally since 1997, with more than half of them fatal. And the concern for wider spread continues to grow. In addition to spreading among cattle in the U.S., H5N1 has spread from wild birds to mammals around the world, including sea lions in South America and mink in Europe. Genetic analysis of two human samples from North America suggested that the virus is adapting and getting better at causing disease and spreading in mammals.

Pitt researchers have long been concerned about the possible spread of avian flu from animals to humans, and have been developing and testing prophylactic interventions -- vaccines and protective antibodies -- in animal models closely resembling humans. In a study published in iScience in 2023, the group reported on further refinements of their aerosol monkey model that closely mimics the symptoms of severe infection with H5N1 in humans, including acute respiratory distress syndrome -- a life-threatening lung injury that can occur upon exposure to bird flu.

One special concern about developing a prophylactic against influenza infections lies in the virus's propensity to quickly adapt to new conditions and environments, the researchers note. Because seasonal flu viruses change and avoid immune responses built up in prior years, an effective seasonal flu vaccine must be reformulated yearly to match the dominant strain. Antibodies targeting the hemagglutinin stalk region that is preserved across different influenza isolates, such as the strain of H5N1 tested in the new study, circumvents the abovementioned challenge and provides broadly neutralizing protection.

"This antibody is targeting a region that does not vary across different influenza viruses," said co-corresponding author Simon Barratt-Boyes, Ph.D., professor of infectious diseases and microbiology at Pitt's School of Public Health and immunology at Pitt's School of Medicine. "Think about it as a tree -- different species have different leaves and crowns, but tree trunks look very much the same. Similarly, the stalk region of the bird flu virus closely resembles the same structure of seasonal influenza, which makes it possible for stalk-targeting antibodies to provide universal protection."

In a new study, monkeys pre-treated with a moderate dose of a broadly neutralizing MEDI8852 antibody were universally protected against severe disease and death. In addition to confirming the antibody's efficacy in preventing serious adverse health outcomes, scientists were also able to establish its minimum serum concentration required for protection -- a measurement useful for establishing the protective threshold of a potential universal flu vaccine.

The research sets the stage for the development of medical countermeasures against future influenza virus pandemics. Serum levels of MEDI8852 sufficient for protection remained stable for 8 to 12 weeks, suggesting that, if given early, it could protect first responders and others caring for patients at the beginning of an outbreak of H5N1.

Masaru Kanekiyo, Ph.D., of the NIH Vaccine Research Center, also contributed to the study. Other authors of this research are affiliated with the NIH Vaccine Research Center, Pitt, UPMC, University of Georgia and AstraZeneca.