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

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Cell Host Microbe. 2019 Nov 1. pii: S1931-3128(19)30527-X. doi: 10.1016/j.chom.2019.10.003. [Epub ahead of print] Influenza H7N9 Virus Neuraminidase-Specific Human Monoclonal Antibodies Inhibit Viral Egress and Protect from Lethal Influenza Infection in Mice.

Gilchuk IM¹, Bangaru S², Gilchuk P¹, Irving RP¹, Kose N¹, Bombardi RG¹, Thornburg NJ¹, Creech CB³, Edwards KM³, Li S⁴, Turner HL⁵, Yu W⁵, Zhu X⁵, Wilson IA⁶, Ward AB⁵, Crowe JE Jr⁷.
Author information

1 The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA. 2 Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. 3 Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA. 4 Department of Medicine, School of Medicine, University of California, San Diego, San Diego, CA 92093, USA. 5 Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. 6 Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. 7 The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: james.crowe@vumc.org.

Abstract

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.
Copyright ? 2019 Elsevier Inc. All rights reserved.


KEYWORDS:

B lymphocyte; H7N9; antibodies; epitopes; influenza A virus; monoclonal; neuraminidase; pre-exposure prophylaxis

PMID: 31757769 DOI: 10.1016/j.chom.2019.10.003