title: H7N9 Live Attenuated Influenza Vaccine Is Highly Immunogenic, Prevents Virus Replication, and Protects Against Severe Bronchopneumonia in Ferrets.
abstract: Avian influenza viruses continue to cross the species barrier, and if such viruses become transmissible among humans, it would pose a great threat to public health. Since its emergence in China in 2013, H7N9 has caused considerable morbidity and mortality. In the absence of a universal influenza vaccine, preparedness includes development of subtype-specific vaccines. In this study, we developed and evaluated in ferrets an intranasal live attenuated influenza vaccine (LAIV) against H7N9 based on the A/Leningrad/134/17/57 (H2N2) cold-adapted master donor virus. We demonstrate that the LAIV is attenuated and safe in ferrets and induces high hemagglutination- and neuraminidase-inhibiting and virus-neutralizing titers. The antibodies against hemagglutinin were also cross-reactive with divergent H7 strains. To assess efficacy, we used an intratracheal challenge ferret model in which an acute severe viral pneumonia is induced that closely resembles viral pneumonia observed in severe human cases. A single- and two-dose strategy provided complete protection against severe pneumonia and prevented virus replication. The protective effect of the two-dose strategy appeared better than the single dose only on the microscopic level in the lungs. We observed, however, an increased lymphocytic infiltration after challenge in single-vaccinated animals and hypothesize that this a side effect of the model.
authors.affiliation: Centre for Infectious Disease Control, National Institute of Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
authors.forename: Jørgen
authors.initials: J
authors.lastname: de Jonge
authors.affiliation: Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.
authors.forename: Irina
authors.initials: I
authors.lastname: Isakova-Sivak
authors.affiliation: Centre for Infectious Disease Control, National Institute of Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: van Dijken
authors.affiliation: Centre for Infectious Disease Control, National Institute of Public Health and the Environment (RIVM), Bilthoven, the Netherlands.|Current address: BioNovion, Oss, the Netherlands.
authors.forename: Sanne
authors.initials: S
authors.lastname: Spijkers
authors.affiliation: Centre for Infectious Disease Control, National Institute of Public Health and the Environment (RIVM), Bilthoven, the Netherlands.|Current address: Genmab, Utrecht, the Netherlands.
authors.forename: Justin
authors.initials: J
authors.lastname: Mouthaan
authors.affiliation: Department of Virology, Central Veterinary Institute of Wageningen UR, Lelystad, the Netherlands.
authors.forename: Rineke
authors.initials: R
authors.lastname: de Jong
authors.affiliation: Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Smolonogina
authors.affiliation: Microscope Consultancy, Weesp, the Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Roholl
authors.affiliation: Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.
authors.forename: Larisa
authors.initials: L
authors.lastname: Rudenko
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral / Q000276:immunology; D001996:Bronchopneumonia / Q000276:immunology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D005289:Ferrets; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000187:drug effects / Q000502:physiology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D014613:Vaccines, Attenuated / Q000008:administration & dosage* / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated