A broadly protective human monoclonal antibody targeting the sialidase activity of influenza A and B virus neuraminidases

• Published in: Nature communications Vol. 13; no. 1; pp. 6602 - 11
• Main Authors: Yasuhara, Atsuhiro, Yamayoshi, Seiya, Kiso, Maki, Sakai-Tagawa, Yuko, Okuda, Moe, Kawaoka, Yoshihiro
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.11.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 631/250/2152/2153/1291; 631/250/255/1578; 631/326/596/1578; 64/60; Antibodies; Antibodies, Monoclonal - pharmacology; Antibodies, Viral; Antigens; Antiviral agents; Antiviral drugs; Binding; Chemical compounds; Epitopes; Exo-a-sialidase; Glycoproteins; Hemagglutinins; Herpesvirus 1, Cercopithecine; Humanities and Social Sciences; Humans; Influenza; Influenza A; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza A Virus, H5N1 Subtype; Influenza A Virus, H7N9 Subtype; Influenza Vaccines; Influenza, Human; Monoclonal antibodies; multidisciplinary; Neuraminidase; Orthomyxoviridae; Orthomyxoviridae Infections; Pharmacology; Science; Science (multidisciplinary); Vaccine development; Vaccines; Viruses
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-34521-0

Improved vaccines and antiviral agents that provide better, broader protection against seasonal and emerging influenza viruses are needed. The viral surface glycoprotein hemagglutinin (HA) is a primary target for the development of universal influenza vaccines and therapeutic antibodies. The other major surface antigen, neuraminidase (NA), has been less well studied as a potential target and fewer broadly reactive anti-NA antibodies have been identified. In this study, we isolate three human monoclonal antibodies that recognize NA from A/H1N1 subtypes, and find that one of them, clone DA03E17, binds to the NA of A/H3N2, A/H5N1, A/H7N9, B/Ancestral-lineage, B/Yamagata-lineage, and B/Victoria-lineage viruses. DA03E17 inhibits the neuraminidase activity by direct binding to the enzyme active site, and provides in vitro and in vivo protection against infection with several types of influenza virus. This clone could, therefore, be useful as a broadly protective therapeutic agent. Moreover, the neutralizing epitope of DA03E17 could be useful in the development of an NA-based universal influenza vaccine. Broadly protective antibodies targeting influenza viruses are of interest as potential therapeutics or to inform vaccine development. Here the authors characterize a human mAb (DA03E17) with heterosubtypic binding to neuraminidases from IAVs and IBVs that provides broad protection in vitro and in vivo.