H7N9 Live Attenuated Influenza Vaccine Is Highly Immunogenic, Prevents Virus Replication, and Protects Against Severe Bronchopneumonia in Ferrets.
Identifieur interne : 000449 ( Main/Merge ); précédent : 000448; suivant : 000450H7N9 Live Attenuated Influenza Vaccine Is Highly Immunogenic, Prevents Virus Replication, and Protects Against Severe Bronchopneumonia in Ferrets.
Auteurs : J Rgen De Jonge [Pays-Bas] ; Irina Isakova-Sivak [Russie] ; Harry Van Dijken [Pays-Bas] ; Sanne Spijkers [Pays-Bas] ; Justin Mouthaan [Pays-Bas] ; Rineke De Jong [Pays-Bas] ; Tatiana Smolonogina [Russie] ; Paul Roholl [Pays-Bas] ; Larisa Rudenko [Russie]Source :
- Molecular therapy : the journal of the American Society of Gene Therapy [ 1525-0024 ] ; 2016.
Descripteurs français
- KwdFr :
- Administration par voie nasale, Animaux, Anticorps antiviraux (immunologie), Anticorps neutralisants, Bronchopneumonie (), Bronchopneumonie (immunologie), Femelle, Furets, Humains, Infections à Orthomyxoviridae (), Infections à Orthomyxoviridae (immunologie), Modèles animaux de maladie humaine, Réplication virale (), Sous-type H7N9 du virus de la grippe A (), Sous-type H7N9 du virus de la grippe A (physiologie), Vaccins antigrippaux (administration et posologie), Vaccins antigrippaux (immunologie), Vaccins atténués (administration et posologie), Vaccins atténués (immunologie).
- MESH :
- administration et posologie : Vaccins antigrippaux, Vaccins atténués.
- immunologie : Anticorps antiviraux, Bronchopneumonie, Infections à Orthomyxoviridae, Vaccins antigrippaux, Vaccins atténués.
- physiologie : Sous-type H7N9 du virus de la grippe A.
- Administration par voie nasale, Animaux, Anticorps neutralisants, Bronchopneumonie, Femelle, Furets, Humains, Infections à Orthomyxoviridae, Modèles animaux de maladie humaine, Réplication virale, Sous-type H7N9 du virus de la grippe A.
English descriptors
- KwdEn :
- Administration, Intranasal, Animals, Antibodies, Neutralizing, Antibodies, Viral (immunology), Bronchopneumonia (immunology), Bronchopneumonia (prevention & control), Disease Models, Animal, Female, Ferrets, Humans, Influenza A Virus, H7N9 Subtype (drug effects), Influenza A Virus, H7N9 Subtype (physiology), Influenza Vaccines (administration & dosage), Influenza Vaccines (immunology), Orthomyxoviridae Infections (immunology), Orthomyxoviridae Infections (prevention & control), Vaccines, Attenuated (administration & dosage), Vaccines, Attenuated (immunology), Virus Replication (drug effects).
- MESH :
- chemical , administration & dosage : Influenza Vaccines, Vaccines, Attenuated.
- chemical , immunology : Antibodies, Viral, Influenza Vaccines, Vaccines, Attenuated.
- chemical : Antibodies, Neutralizing.
- drug effects : Influenza A Virus, H7N9 Subtype, Virus Replication.
- immunology : Bronchopneumonia, Orthomyxoviridae Infections.
- physiology : Influenza A Virus, H7N9 Subtype.
- prevention & control : Bronchopneumonia, Orthomyxoviridae Infections.
- Administration, Intranasal, Animals, Disease Models, Animal, Female, Ferrets, Humans.
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.
DOI: 10.1038/mt.2016.23
PubMed: 26796670
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<term>Animals</term>
<term>Antibodies, Neutralizing</term>
<term>Antibodies, Viral (immunology)</term>
<term>Bronchopneumonia (immunology)</term>
<term>Bronchopneumonia (prevention & control)</term>
<term>Disease Models, Animal</term>
<term>Female</term>
<term>Ferrets</term>
<term>Humans</term>
<term>Influenza A Virus, H7N9 Subtype (drug effects)</term>
<term>Influenza A Virus, H7N9 Subtype (physiology)</term>
<term>Influenza Vaccines (administration & dosage)</term>
<term>Influenza Vaccines (immunology)</term>
<term>Orthomyxoviridae Infections (immunology)</term>
<term>Orthomyxoviridae Infections (prevention & control)</term>
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<term>Vaccines, Attenuated (immunology)</term>
<term>Virus Replication (drug effects)</term>
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<term>Animaux</term>
<term>Anticorps antiviraux (immunologie)</term>
<term>Anticorps neutralisants</term>
<term>Bronchopneumonie ()</term>
<term>Bronchopneumonie (immunologie)</term>
<term>Femelle</term>
<term>Furets</term>
<term>Humains</term>
<term>Infections à Orthomyxoviridae ()</term>
<term>Infections à Orthomyxoviridae (immunologie)</term>
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<term>Vaccins atténués (administration et posologie)</term>
<term>Vaccins atténués (immunologie)</term>
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<term>Infections à Orthomyxoviridae</term>
<term>Vaccins antigrippaux</term>
<term>Vaccins atténués</term>
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<front><div type="abstract" xml:lang="en">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.</div>
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