Serveur d'exploration H2N2

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Live, Attenuated Influenza A H5N1 Candidate Vaccines Provide Broad Cross-Protection in Mice and Ferrets

Identifieur interne : 001476 ( Main/Exploration ); précédent : 001475; suivant : 001477

Live, 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 :

RBID : PMC:1564176

Descripteurs français

English descriptors

Abstract

Background

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.

Methods and Findings

Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA) and a wild-type (wt) 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 (ca) influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 ca (H2N2), were generated by reverse genetics. The H5N1 ca 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 ca vaccine donor strain. More importantly, the candidate vaccines were immunogenic in mice. Four weeks after receiving a single dose of 106 50% tissue culture infectious doses of intranasally administered vaccines, mice were fully protected from lethality following challenge with homologous and antigenically distinct heterologous wt 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 wt H5N1 viruses.

Conclusions

The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1 ca vaccines against antigenically diverse H5N1 vaccines provide support for their careful evaluation in Phase 1 clinical trials in humans.


Url:
DOI: 10.1371/journal.pmed.0030360
PubMed: 16968127
PubMed Central: 1564176


Affiliations:


Links toward previous steps (curation, corpus...)


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<name sortKey="Murphy, Brian" sort="Murphy, Brian" uniqKey="Murphy B" first="Brian" last="Murphy">Brian Murphy</name>
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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>
</front>
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<name sortKey="Mendelman, Pm" uniqKey="Mendelman P">PM Mendelman</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Belshe, Rb" uniqKey="Belshe R">RB Belshe</name>
</author>
<author>
<name sortKey="Gruber, Wc" uniqKey="Gruber W">WC Gruber</name>
</author>
<author>
<name sortKey="Mendelman, Pm" uniqKey="Mendelman P">PM Mendelman</name>
</author>
<author>
<name sortKey="Cho, I" uniqKey="Cho I">I Cho</name>
</author>
<author>
<name sortKey="Reisinger, K" uniqKey="Reisinger K">K Reisinger</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Steinhauer, Da" uniqKey="Steinhauer D">DA Steinhauer</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<affiliations>
<list>
<country>
<li>États-Unis</li>
</country>
<region>
<li>Californie</li>
<li>Géorgie (États-Unis)</li>
<li>Maryland</li>
</region>
</list>
<tree>
<country name="États-Unis">
<region name="Maryland">
<name sortKey="Suguitan, Amorsolo L" sort="Suguitan, Amorsolo L" uniqKey="Suguitan A" first="Amorsolo L" last="Suguitan">Amorsolo L. Suguitan</name>
</region>
<name sortKey="Duke, Greg" sort="Duke, Greg" uniqKey="Duke G" first="Greg" last="Duke">Greg Duke</name>
<name sortKey="Jin, Hong" sort="Jin, Hong" uniqKey="Jin H" first="Hong" last="Jin">Hong Jin</name>
<name sortKey="Kemble, George" sort="Kemble, George" uniqKey="Kemble G" first="George" last="Kemble">George Kemble</name>
<name sortKey="Lu, Bin" sort="Lu, Bin" uniqKey="Lu B" first="Bin" last="Lu">Bin Lu</name>
<name sortKey="Luke, Catherine J" sort="Luke, Catherine J" uniqKey="Luke C" first="Catherine J" last="Luke">Catherine J. Luke</name>
<name sortKey="Mcauliffe, Josephine" sort="Mcauliffe, Josephine" uniqKey="Mcauliffe J" first="Josephine" last="Mcauliffe">Josephine Mcauliffe</name>
<name sortKey="Mills, Kimberly L" sort="Mills, Kimberly L" uniqKey="Mills K" first="Kimberly L" last="Mills">Kimberly L. Mills</name>
<name sortKey="Murphy, Brian" sort="Murphy, Brian" uniqKey="Murphy B" first="Brian" last="Murphy">Brian Murphy</name>
<name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name>
<name sortKey="Swayne, David E" sort="Swayne, David E" uniqKey="Swayne D" first="David E" last="Swayne">David E. Swayne</name>
</country>
</tree>
</affiliations>
</record>

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