By IDSE News Staff
A prophylactic antibody-based immunotherapy protects macaques against severe disease caused by H5N1 avian flu, according to University of Pittsburgh and National Institute of Allergy and Infectious Diseases Vaccine Research Center researchers (Science 2025;387[6733]: 534 doi:10.1126/science.ado6481).
Influenza viruses have a propensity to quickly adapt to new conditions and environments, the researchers noted, which increases the challenge in developing a prophylactic medication. 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, PhD, a professor of infectious diseases and microbiology at Pitt Public Health and of immunology at the University of Pittsburgh 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 [virus], which makes it possible for stalk-targeting antibodies to provide universal protection.”
In the 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 established its minimum serum concentration required for protection.
The broadly neutralizing antibody, which recognizes a relatively stable region of the avian influenza 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 variants and provide lasting protection against a globally spreading airborne infection, the researchers said.
“This type of prevention can be very useful in controlling infection outbreaks and containing the bird flu pandemic,” said co-corresponding author Douglas Reed, PhD, an associate professor of immunology at the Pitt 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.”
Although only one reported case of H5N1 infection in the UnitedStates has resulted in death, so far, the WHO has reported more than 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 United States, 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 the virus is adapting and getting better at spreading and causing disease 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. 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.
Serum levels of MEDI8852 sufficient for protection remained stable for eight 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, PhD, of the Vaccine Research Center at the NIAID, 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.
