title: An influenza A virus (H7N9) anti-neuraminidase monoclonal antibody with prophylactic and therapeutic activity in vivo.
abstract: Zoonotic A(H7N9) avian influenza viruses emerged in China in 2013 and continue to be a threat to human public health, having infected over 800 individuals with a mortality rate approaching 40%. Treatment options for people infected with A(H7N9) include the use of neuraminidase (NA) inhibitors. However, like other influenza viruses, A(H7N9) can become resistant to these drugs. The use of monoclonal antibodies is a rapidly developing strategy for controlling influenza virus infection. Here we generated a murine monoclonal antibody (3c10-3) directed against the NA of A(H7N9) and show that prophylactic systemic administration of 3c10-3 fully protected mice from lethal challenge with wild-type A/Anhui/1/2013 (H7N9). Further, post-infection treatment with a single systemic dose of 3c10-3 at either 24, 48 or 72 h post A(H7N9) challenge resulted in both dose- and time-dependent protection of up to 100% of mice, demonstrating therapeutic potential for 3c10-3. Epitope mapping revealed that 3c10-3 binds near the enzyme active site of NA, and functional characterization showed that 3c10-3 inhibits the enzyme activity of NA and restricts the cell-to-cell spread of the virus in cultured cells. Affinity analysis also revealed that 3c10-3 binds equally well to recombinant NA of wild-type A/Anhui/1/2013 and to a variant NA carrying a R289K mutation known to infer NAI resistance. These results suggest that 3c10-3 has the potential to be used as a therapeutic to treat A(H7N9) infections either as an alternative to, or in combination with, current NA antiviral inhibitors.
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA, USA; Carter Consulting, Inc., Atlanta, GA, USA.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Wilson
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Adrian
authors.initials: A
authors.lastname: Reber
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA, USA; Battelle Memorial Institute, Atlanta, GA, USA.
authors.forename: Ram P
authors.initials: RP
authors.lastname: Kamal
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA, USA; Battelle Memorial Institute, Atlanta, GA, USA.
authors.forename: Nedzad
authors.initials: N
authors.lastname: Music
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA, USA; Carter Consulting, Inc., Atlanta, GA, USA.
authors.forename: Shane
authors.initials: S
authors.lastname: Gansebom
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Yaohui
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Levine
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Carney
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Wen-Pin
authors.initials: WP
authors.lastname: Tzeng
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Stevens
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA, USA. Electronic address: ite1@cdc.gov.
authors.forename: Ian A
authors.initials: IA
authors.lastname: York
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D020134:Catalytic Domain; D002681:China; D024882:Drug Resistance, Viral; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000201:enzymology / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control / Q000628:therapy; D051379:Mice; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy* / Q000821:virology; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology*; D014779:Virus Replication
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D014764:Viral Proteins; C487630:NA protein, influenza A virus; D009439:Neuraminidase
keywords: Antiviral; H7N9; Influenza; Monoclonal antibody; NA epitope; Neuraminidase