title: Passive immunization with a recombinant adenovirus expressing an HA (H5)-specific single-domain antibody protects mice from lethal influenza infection.
abstract: One effective method for the prevention and treatment of influenza infection is passive immunization. In our study, we examined the feasibility of creating an antibody-based preparation with a prolonged protective effect against influenza virus. Single-domain antibodies (sdAbs) specific for influenza virus hemagglutinin were generated. Experiments in mouse models showed 100% survivability for both intranasal sdAbs administration 24h prior to influenza challenge and 24h after infection. sdAb-gene delivery by an adenoviral vector led to gene expression for up to 14days. Protection by a recombinant adenovirus containing the sdAb gene was observed in cases of administration prior to influenza infection (14d-24h). We also demonstrated that the single administration of a combined preparation containing sdAb DNA and protein expanded the protection time window from 14d prior to 48h after influenza infection. This approach and the application of a broad-spectrum sdAbs will allow the development of efficient drugs for the prevention and treatment of viral infections produced by pandemic virus variants and other infections.
authors.affiliation: Gamaleya Research Institute for Epidemiology and Microbiology, 18, Gamaleya Street, Moscow 123098, Russia.
authors.forename: Irina L
authors.initials: IL
authors.lastname: Tutykhina
authors.forename: Elena S
authors.initials: ES
authors.lastname: Sedova
authors.forename: Irina Y
authors.initials: IY
authors.lastname: Gribova
authors.forename: Tatiana I
authors.initials: TI
authors.lastname: Ivanova
authors.forename: Lev A
authors.initials: LA
authors.lastname: Vasilev
authors.forename: Marina V
authors.initials: MV
authors.lastname: Rutovskaya
authors.forename: Andrei A
authors.initials: AA
authors.lastname: Lysenko
authors.forename: Maxim M
authors.initials: MM
authors.lastname: Shmarov
authors.forename: Denis Y
authors.initials: DY
authors.lastname: Logunov
authors.forename: Boris S
authors.initials: BS
authors.lastname: Naroditsky
authors.forename: Sergei V
authors.initials: SV
authors.lastname: Tillib
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Gintsburg
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000235:genetics* / Q000276:immunology*; D002460:Cell Line; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D007116:Immunization, Passive; D053125:Influenza A Virus, H5N2 Subtype / Q000235:genetics / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D061905:Single-Domain Antibodies / Q000235:genetics* / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D061905:Single-Domain Antibodies