Live, Attenuated Influenza A H5N1 Candidate Vaccines Provide Broad Cross-Protection in Mice and Ferrets
Identifieur interne : 000184 ( Ncbi/Curation ); précédent : 000183; suivant : 000185Live, Attenuated Influenza A H5N1 Candidate Vaccines Provide Broad Cross-Protection in Mice and Ferrets
Auteurs : Amorsolo L. Suguitan [États-Unis] ; Josephine Mcauliffe [États-Unis] ; Kimberly L. Mills [États-Unis] ; Hong Jin [États-Unis] ; Greg Duke [États-Unis] ; Bin Lu [États-Unis] ; Catherine J. Luke [États-Unis] ; Brian Murphy [États-Unis] ; David E. Swayne [États-Unis] ; George Kemble [États-Unis] ; Kanta Subbarao [États-Unis]Source :
- PLoS Medicine [ 1549-1277 ] ; 2006.
Descripteurs français
- KwdFr :
- Animaux, Calendrier vaccinal, Femelle, Furets, Grippe chez les oiseaux (), Grippe chez les oiseaux (immunologie), Grippe chez les oiseaux (virologie), Poulets, Souris, Souris de lignée BALB C, Sous-type H5N1 du virus de la grippe A (génétique), Sous-type H5N1 du virus de la grippe A (immunologie), Vaccins antigrippaux (génétique), Vaccins antigrippaux (immunologie), Vaccins antigrippaux (usage thérapeutique), Vaccins atténués (génétique), Vaccins atténués (immunologie), Vaccins atténués (usage thérapeutique), Évaluation préclinique de médicament ().
- MESH :
- génétique : Sous-type H5N1 du virus de la grippe A, Vaccins antigrippaux, Vaccins atténués.
- immunologie : Grippe chez les oiseaux, Sous-type H5N1 du virus de la grippe A, Vaccins antigrippaux, Vaccins atténués.
- usage thérapeutique : Vaccins antigrippaux, Vaccins atténués.
- virologie : Grippe chez les oiseaux.
- Animaux, Calendrier vaccinal, Femelle, Furets, Grippe chez les oiseaux, Poulets, Souris, Souris de lignée BALB C, Évaluation préclinique de médicament.
English descriptors
- KwdEn :
- Animals, Chickens, Drug Evaluation, Preclinical (methods), Female, Ferrets, Immunization Schedule, Influenza A Virus, H5N1 Subtype (genetics), Influenza A Virus, H5N1 Subtype (immunology), Influenza Vaccines (genetics), Influenza Vaccines (immunology), Influenza Vaccines (therapeutic use), Influenza in Birds (immunology), Influenza in Birds (prevention & control), Influenza in Birds (virology), Mice, Mice, Inbred BALB C, Vaccines, Attenuated (genetics), Vaccines, Attenuated (immunology), Vaccines, Attenuated (therapeutic use).
- MESH :
- chemical , genetics : Influenza Vaccines, Vaccines, Attenuated.
- genetics : Influenza A Virus, H5N1 Subtype.
- immunology : Influenza A Virus, H5N1 Subtype, Influenza Vaccines, Influenza in Birds, Vaccines, Attenuated.
- methods : Drug Evaluation, Preclinical.
- prevention & control : Influenza in Birds.
- chemical , therapeutic use : Influenza Vaccines, Vaccines, Attenuated.
- virology : Influenza in Birds.
- Animals, Chickens, Female, Ferrets, Immunization Schedule, Mice, Mice, Inbred BALB C.
Abstract
Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species that began in Asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic.
Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA) and a wild-type
The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1
Url:
DOI: 10.1371/journal.pmed.0030360
PubMed: 16968127
PubMed Central: 1564176
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PMC:1564176Le document en format XML
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<front><div type="abstract" xml:lang="en"><sec id="st1"><title>Background</title>
<p>Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species that began in Asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic.</p>
</sec>
<sec id="st2"><title>Methods and Findings</title>
<p>Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA) and a wild-type <italic>(wt)</italic>
N1 neuraminidase from influenza A H5N1 viruses isolated in Hong Kong and Vietnam in 1997, 2003, and 2004, and remaining gene segments derived from the cold-adapted <italic>(ca)</italic>
influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 <italic>ca</italic>
(H2N2), were generated by reverse genetics. The H5N1 <italic>ca</italic>
vaccine viruses required trypsin for efficient growth in vitro, as predicted by the modification engineered in the gene encoding the HA, and possessed the temperature-sensitive and attenuation phenotypes specified by the internal protein genes of the <italic>ca</italic>
vaccine donor strain. More importantly, the candidate vaccines were immunogenic in mice. Four weeks after receiving a single dose of 10<sup>6</sup>
50% tissue culture infectious doses of intranasally administered vaccines, mice were fully protected from lethality following challenge with homologous and antigenically distinct heterologous <italic>wt</italic>
H5N1 viruses from different genetic sublineages (clades 1, 2, and 3) that were isolated in Asia between 1997 and 2005. Four weeks after receiving two doses of the vaccines, mice and ferrets were fully protected against pulmonary replication of homologous and heterologous <italic>wt</italic>
H5N1 viruses.</p>
</sec>
<sec id="st3"><title>Conclusions</title>
<p>The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1 <italic>ca</italic>
vaccines against antigenically diverse H5N1 vaccines provide support for their careful evaluation in Phase 1 clinical trials in humans.</p>
</sec>
</div>
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