Antibodies provide protection against highly pathogenic avian influenza subtype H5N1 in monkeys
Prof. Dr. Salah Mahdi Hassan /Consultant and poultry health expert
Outbreaks of influenza viruses and seasonal epidemics have been major threats to global public health, resulting in many deaths each year. The frequent spread of highly pathogenic avian influenza viruses, represented by subtype H5 and H7 viruses, which have the potential to transmit infections between humans, underscores the urgent need for effective preventive measures.
In this context, researchers at the University of Pittsburgh and the NIH Vaccine Research Center announced, through their new scientific research published in the journal Science on 1/31/2025, the possibility of using the broadly neutralizing antibody (bnAb) MEDI8852 as a preventive treatment in cynomolgus macaques, against the risk of severe symptoms caused by respiratory infection with the highly pathogenic avian influenza virus H5N1.
It is worth noting that the broadly neutralizing antibody (bnAb) MEDI8852 is a monoclonal antibody specifically designed to target the epitopes on the (HA) protein of influenza viruses. The purpose of its production is to seek to provide broader protection against multiple subtypes of influenza A viruses, including highly pathogenic avian influenza (HPAI) variants of the H5N1 subtype. In that broadly neutralizing antibodies (bnAb), which target a relatively stable region of the avian influenza virus, are less likely to lose their immunogenicity than antibodies that target the entire influenza virus structure, which in turn are often susceptible to genetic mutations.
This advantage provides the ability to protect against the potential emergence of virus variants, such as the SARS-CoV-2 mutations that have evolved during the COVID-19 pandemic, as well as to provide lasting protection against global respiratory infections. This study showed that prophylactic treatment with the broadly neutralizing antibody (bnAb) MEDI8852 prior to exposure to highly pathogenic avian influenza virus was highly effective in protecting cynomolgus macaques from severe pathological effects caused by highly pathogenic avian influenza virus H5N1 infection. The study also showed that this protection was dependent on the dose of neutralizing antibodies used, while indicating at the same time that this protection was independent of the effects of activities produced at the Fc terminus and for all doses used. The study did not observe any deviation in the action of antibodies after administration of viral sequence mutations, indicating that prophylactic treatment with these broadly neutralizing antibodies is not selective for specific viral variants that could affect its efficacy, confirming its broad therapeutic and prophylactic range.
This study indicated that macaques given neutralizing antibodies MEDI8852 at a dose of 10 mg/kg or higher showed no significant impairment of respiratory function after infection, compared with untreated control animals infected with H5N1, which showed severe signs of avian influenza and mortality.
The World Health Organization (WHO) has reported more than 950 human cases of avian influenza worldwide since 1997, more than half of which were fatal, and the latest reported case of a fatal H5N1 infection by U.S. authorities in January 2025. Concerns remain about the widespread outbreaks of H5N1, which are reported periodically by the World Organization for Animal Health (WOAH). In addition to its spread among cattle in the United States, H5N1 has spread from wild birds to mammals worldwide, including sea lions in South America and mink in Europe. Genetic analysis of two human samples from North America suggests that the virus is adapting and becoming more capable of causing disease and spreading in mammals.
Researchers at the University of Pittsburgh have long been concerned about the potential for avian influenza to spread from animals to humans, and have been working to develop and test preventive interventions (through vaccines and protective antibodies) in animal species that closely resemble humans. In a study by researchers from this university, also published in the journal Science in 2023, they revealed further improvements to an experimental model of a monkey infected through the respiratory system that closely resembles the symptoms of severe H5N1 infection in humans, including acute respiratory distress syndrome, a life-threatening lung infection that can occur with exposure to avian influenza.
The researchers pointed out that one of the particular concerns about developing a preventive treatment for influenza infection lies in the virus’s tendency to adapt quickly to new environmental conditions, which leads to mutations and viral variants. Because seasonal influenza viruses change and avoid the immune responses accumulated in previous years, an effective seasonal influenza vaccine must be reproduced annually to match the dominant strain of the virus.
Therefore, because antibodies that target the HA stem region that is conserved across different influenza isolates, such as the H5N1 strain tested in this new study, overcome the above-mentioned challenge and provide adequate and broad protection. These antibodies target a region of the virus antigen that does not differ between different influenza viruses. Similarly, the stalk region of the avian influenza virus is very similar in structure to seasonal influenza, making it possible for antibodies targeting the stalk to provide broad protection against all types of influenza.
In addition to confirming the effectiveness of the neutralizing antibody bnAb in preventing severe disease symptoms of H5N1, the study was also able to determine the minimum concentration of these antibodies required for protection in the serum, a useful measure for determining the protective threshold for a potential universal influenza vaccine.
All of this, this study and valuable research appear to pave the way for developing strategies to prevent future influenza outbreaks and to work on medical countermeasures for outbreaks of highly pathogenic avian influenza viruses. Because this study indicated that the levels of neutralizing antibodies MEDI8852 sufficient for protection remained stable for 8 to 12 weeks, this suggests that, if given early, it could protect infected people and other caregivers. From doctors and nurses at the beginning of the H5N1 outbreak.
To view the study mentioned:
Pre-exposure antibody prophylaxis protects macaques from severe influenza
Masaru Kanekiyo et.al. ( 2025) , Science;387(6733):534-541. doi: 10.1126/science.ado6481. Epub 2025 Jan 30
