A Human Antibody Recognizing a Conserved Epitope of H5 Hemagglutinin Broadly Neutralizes Highly Pathogenic Avian Influenza H5N1 Viruses

Influenza A virus infection is a persistent threat to public health worldwide due to its ability to evade immune surveillance through rapid genetic drift and shift. Current vaccines against influenza A virus provide immunity to viral isolates that are simi-lar to vaccine strains. High-affinity neutralizing antibodies against conserved epitopes could provide immunity to diverse influ-enza virus strains and protection against future pandemic viruses. In this study, by using a highly sensitive H5N1 pseudotype-based neutralization assay to screen humanmonoclonal antibodies produced by memory B cells from an H5N1-infected individual andmolecular cloning techniques, we developed three fully humanmonoclonal antibodies. Among them, antibody 65C6 exhibited potent neutralization activity against all H5 clades and subclades except for subclade 7.2 and prophylactic and therapeutic efficacy against highly pathogenic avian influenza H5N1 viruses in mice. Studies on hemagglutinin (HA)-antibody complexes by electronmicroscopy and epitope mapping indicate that antibody 65C6 binds to a conformational epitope compris