H7N9 Live Attenuated Influenza Vaccine Is Highly Immunogenic, Prevents Virus Replication, and Protects Against Severe Bronchopneumonia in Ferrets.
Identifieur interne : 000054 ( PubMed/Corpus ); précédent : 000053; suivant : 000055H7N9 Live Attenuated Influenza Vaccine Is Highly Immunogenic, Prevents Virus Replication, and Protects Against Severe Bronchopneumonia in Ferrets.
Auteurs : J Rgen De Jonge ; Irina Isakova-Sivak ; Harry Van Dijken ; Sanne Spijkers ; Justin Mouthaan ; Rineke De Jong ; Tatiana Smolonogina ; Paul Roholl ; Larisa RudenkoSource :
- Molecular therapy : the journal of the American Society of Gene Therapy [ 1525-0024 ] ; 2016.
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
Links to Exploration step
pubmed:26796670Le document en format XML
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Animal</term><term>Female</term><term>Ferrets</term><term>Humans</term></keywords></textClass></profileDesc></teiHeader><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></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26796670</PMID><DateCompleted><Year>2017</Year><Month>06</Month><Day>16</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1525-0024</ISSN><JournalIssue CitedMedium="Internet"><Volume>24</Volume><Issue>5</Issue><PubDate><Year>2016</Year><Month>05</Month></PubDate></JournalIssue><Title>Molecular therapy : the journal of the American Society of Gene Therapy</Title><ISOAbbreviation>Mol. Ther.</ISOAbbreviation></Journal><ArticleTitle>H7N9 Live Attenuated Influenza Vaccine Is Highly Immunogenic, Prevents Virus Replication, and Protects Against Severe Bronchopneumonia in Ferrets.</ArticleTitle><Pagination><MedlinePgn>991-1002</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/mt.2016.23</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>de Jonge</LastName><ForeName>Jørgen</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Centre for Infectious Disease Control, National Institute of Public Health and the Environment (RIVM), Bilthoven, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Isakova-Sivak</LastName><ForeName>Irina</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>van Dijken</LastName><ForeName>Harry</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Centre for Infectious Disease Control, National Institute of Public Health and the Environment (RIVM), Bilthoven, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Spijkers</LastName><ForeName>Sanne</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Centre for Infectious Disease Control, National Institute of Public Health and the Environment (RIVM), Bilthoven, the Netherlands.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Current address: BioNovion, Oss, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mouthaan</LastName><ForeName>Justin</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Centre for Infectious Disease Control, National Institute of Public Health and the Environment (RIVM), Bilthoven, the Netherlands.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Current address: Genmab, Utrecht, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>de Jong</LastName><ForeName>Rineke</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Virology, Central Veterinary Institute of Wageningen UR, Lelystad, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Smolonogina</LastName><ForeName>Tatiana</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Roholl</LastName><ForeName>Paul</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Microscope Consultancy, Weesp, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rudenko</LastName><ForeName>Larisa</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>01</Month><Day>22</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Mol Ther</MedlineTA><NlmUniqueID>100890581</NlmUniqueID><ISSNLinking>1525-0016</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D057134">Antibodies, Neutralizing</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000914">Antibodies, Viral</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007252">Influenza Vaccines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014613">Vaccines, Attenuated</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000281" MajorTopicYN="N">Administration, Intranasal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D057134" MajorTopicYN="N">Antibodies, Neutralizing</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000914" MajorTopicYN="N">Antibodies, Viral</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001996" MajorTopicYN="N">Bronchopneumonia</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000517" MajorTopicYN="Y">prevention & control</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005289" MajorTopicYN="N">Ferrets</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D064766" MajorTopicYN="N">Influenza A Virus, H7N9 Subtype</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007252" MajorTopicYN="N">Influenza Vaccines</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009976" MajorTopicYN="N">Orthomyxoviridae Infections</DescriptorName><QualifierName UI="Q000276" 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