A human monoclonal antibody targeting the monomeric N6 neuraminidase confers protection against avian H5N6 influenza virus infection

• Published in: Nature communications Vol. 15; no. 1; pp. 8871 - 11
• Main Authors: Wang, Min, Gao, Yuan, Shen, Chenguang, Yang, Wei, Peng, Qi, Cheng, Jinlong, Shen, Han-Ming, Yang, Yang, Gao, George Fu, Shi, Yi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.10.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 101/1; 101/28; 38/109; 631/250/2152/2153/1291; 631/326/596/1578; 631/535/1258/1259; 64/60; 82/80; 82/83; Animals; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - immunology; Antibodies, Viral - immunology; Antibody response; Antigenicity; Avian flu; Birds - virology; Cryoelectron Microscopy; Enzymatic activity; Epitopes; Epitopes - immunology; Exo-a-sialidase; Female; Females; Humanities and Social Sciences; Humans; Immune response; Influenza; Influenza A virus - immunology; Influenza in Birds - immunology; Influenza in Birds - prevention & control; Influenza in Birds - virology; Influenza Vaccines - immunology; Influenza, Human - immunology; Influenza, Human - prevention & control; Influenza, Human - virology; Mice; Mice, Inbred BALB C; Molecular structure; Monoclonal antibodies; multidisciplinary; Neuraminidase - chemistry; Neuraminidase - immunology; Neuraminidase - metabolism; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - prevention & control; Orthomyxoviridae Infections - virology; Science; Science (multidisciplinary); Structure-function relationships; Vaccines; Viral Proteins - chemistry; Viral Proteins - immunology; Viral Proteins - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-53301-6

The influenza neuraminidase (NA) is a potential target for the development of a next-generation influenza vaccine, but its antigenicity is not well understood. Here, we isolate an anti-N6 human monoclonal antibody, named 18_14D, from an H5N6 avian influenza virus (AIV) infected patient. The antibody weakly inhibits enzymatic activity but confers protection in female mice, mainly via ADCC function. The cryo-EM structure shows that 18_14D binds to a unique epitope on the lateral surface of the N6 tetramer, preventing the formation of tightly closed NA tetramers. These findings contribute to the molecular understanding of protective immune responses to NA of AIVs in humans and open an avenue for the rational design of NA-based vaccines. Understanding the antibody response to influenza neuraminidase (NA) can identify protective epitopes. Here, the authors isolate an antibody from an H5N6 infected patient, characterize the epitope on the N6 tetramer, and show that it’s protective in female mice.