Influenza H7N9 Virus Neuraminidase-Specific Human Monoclonal Antibodies Inhibit Viral Egress and Protect from Lethal Influenza Infection in Mice

• Published in: Cell host & microbe Vol. 26; no. 6; pp. 715 - 728.e8
• Main Authors: Gilchuk, Iuliia M., Bangaru, Sandhya, Gilchuk, Pavlo, Irving, Ryan P., Kose, Nurgun, Bombardi, Robin G., Thornburg, Natalie J., Creech, C. Buddy, Edwards, Kathryn M., Li, Sheng, Turner, Hannah L., Yu, Wenli, Zhu, Xueyong, Wilson, Ian A., Ward, Andrew B., Crowe, James E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.12.2019
• Subjects: Animals; antibodies; Antibodies, Heterophile - pharmacology; Antibodies, Monoclonal - pharmacology; Antibodies, Neutralizing - pharmacology; Antibodies, Viral - pharmacology; B lymphocyte; Birds; epitopes; Epitopes - immunology; H7N9; Humans; influenza A virus; Influenza A Virus, H7N9 Subtype - drug effects; Influenza A Virus, H7N9 Subtype - immunology; Influenza in Birds - prevention & control; Influenza in Birds - virology; Influenza Vaccines - immunology; Influenza, Human - prevention & control; Influenza, Human - virology; Mice; monoclonal; neuraminidase; Neuraminidase - immunology; Orthomyxoviridae Infections - prevention & control; Orthomyxoviridae Infections - virology; Pre-Exposure Prophylaxis; Vaccination; Vaccines, Inactivated; Viral Proteins - immunology; Virus Release - drug effects; epitopes; pre-exposure prophylaxis; neuraminidase; B lymphocyte; antibodies; monoclonal; H7N9; influenza A virus
• ISSN: 1931-3128; 1934-6069; 1934-6069
• DOI: 10.1016/j.chom.2019.10.003

H7N9 avian influenza virus causes severe infections and might have the potential to trigger a major pandemic. Molecular determinants of human humoral immune response to N9 neuraminidase (NA) proteins, which exhibit unusual features compared with seasonal influenza virus NA proteins, are ill-defined. We isolated 35 human monoclonal antibodies (mAbs) from two H7N9 survivors and two vaccinees. These mAbs react to NA in a subtype-specific manner and recognize diverse antigenic sites on the surface of N9 NA, including epitopes overlapping with, or distinct from, the enzyme active site. Despite recognizing multiple antigenic sites, the mAbs use a common mechanism of action by blocking egress of nascent virions from infected cells, thereby providing an antiviral prophylactic and therapeutic protection in vivo in mice. Studies of breadth, potency, and diversity of antigenic recognition from four subjects suggest that vaccination with inactivated adjuvanted vaccine induce NA-reactive responses comparable to that of H7N9 natural infection. [Display omitted] •Human mAbs recognize several antigenic sites on influenza virus N9 NA•The mAbs act by blocking egress of nascent virions from infected cells•Human mAbs mediate prophylactic and therapeutic protection in vivo in mice•Protection is mediated by direct virus neutralization or Fc-region effector function Molecular determinants of the human B cell response to avian influenza N9 neuraminidase (NA) proteins, which differ from seasonal virus NAs, are ill-defined. Gilchuk et al. identify antibodies to multiple protective antigenic sites on N9 NA that block egress of nascent virions from infected cells and mediate protection in mice.