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Passive immunization with a recombinant adenovirus expressing an HA (H5)-specific single-domain antibody protects mice from lethal influenza infection

Identifieur interne : 000216 ( PascalFrancis/Checkpoint ); précédent : 000215; suivant : 000217

Passive immunization with a recombinant adenovirus expressing an HA (H5)-specific single-domain antibody protects mice from lethal influenza infection

Auteurs : Irina L. Tutykhina [Russie] ; Elena S. Sedova [Russie] ; Irina Y. Gribova [Russie] ; Tatiana I. Ivanova [Russie] ; Lev A. Vasilev [Russie] ; Marina V. Rutovskaya [Russie] ; Andrei A. Lysenko [Russie] ; Maxim M. Shmarov [Russie] ; Denis Y. Logunov [Russie] ; Boris S. Naroditsky [Russie] ; Sergei V. Tillib [Russie] ; Alexander L. Gintsburg [Russie]

Source :

RBID : Pascal:13-0152042

Descripteurs français

English descriptors

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 hem-agglutinin were generated. Experiments in mouse models showed 100% survivability for both intranasal sdAbs administration 24 h prior to influenza challenge and 24 h after infection. sdAb-gene delivery by an adenoviral vector led to gene expression for up to 14 days. Protection by a recombinant adenovirus containing the sdAb gene was observed in cases of administration prior to influenza infection (14 d-24 h). We also demonstrated that the single administration of a combined preparation containing sdAb DNA and protein expanded the protection time window from 14 d prior to 48 h 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.


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Pascal:13-0152042

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<title level="j" type="main">Antiviral research</title>
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<idno type="ISSN">0166-3542</idno>
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<term>Adenoviridae</term>
<term>Animal</term>
<term>Antibody</term>
<term>Human adenovirus</term>
<term>Influenza</term>
<term>Influenzavirus</term>
<term>Mouse</term>
<term>Passive immunization</term>
<term>Prevention</term>
<term>Vector</term>
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<term>Immunisation passive</term>
<term>Adenoviridae</term>
<term>Adénovirus humain</term>
<term>Anticorps</term>
<term>Prévention</term>
<term>Animal</term>
<term>Souris</term>
<term>Grippe</term>
<term>Influenzavirus</term>
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<div type="abstract" xml:lang="en">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 hem-agglutinin were generated. Experiments in mouse models showed 100% survivability for both intranasal sdAbs administration 24 h prior to influenza challenge and 24 h after infection. sdAb-gene delivery by an adenoviral vector led to gene expression for up to 14 days. Protection by a recombinant adenovirus containing the sdAb gene was observed in cases of administration prior to influenza infection (14 d-24 h). We also demonstrated that the single administration of a combined preparation containing sdAb DNA and protein expanded the protection time window from 14 d prior to 48 h 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.</div>
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