Evaluation of Live Attenuated Influenza A Virus H6 Vaccines in Mice and Ferrets▿
Identifieur interne : 000331 ( Ncbi/Merge ); précédent : 000330; suivant : 000332Evaluation of Live Attenuated Influenza A Virus H6 Vaccines in Mice and Ferrets▿
Auteurs : Zhongying Chen ; Celia Santos ; Amy Aspelund ; Laura Gillim-Ross ; Hong Jin ; George Kemble ; Kanta SubbaraoSource :
- Journal of Virology [ 0022-538X ] ; 2008.
Abstract
Avian influenza A virus A/teal/HK/W312/97 (H6N1) possesses seven gene segments that are highly homologous to those of highly pathogenic human influenza H5N1 viruses, suggesting that a W312-like H6N1 virus might have been involved in the generation of the A/HK/97 H5N1 viruses. The continuous circulation and reassortment of influenza H6 subtype viruses in birds highlight the need to develop an H6 vaccine to prevent potential influenza pandemics caused by the H6 viruses. Based on the serum antibody cross-reactivity data obtained from 14 different H6 viruses from Eurasian and North American lineages, A/duck/HK/182/77, A/teal/HK/W312/97, and A/mallard/Alberta/89/85 were selected to produce live attenuated H6 candidate vaccines. Each of the H6 vaccine strains is a 6:2 reassortant
Url:
DOI: 10.1128/JVI.01775-08
PubMed: 18945773
PubMed Central: 2612304
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000367
- to stream Pmc, to step Curation: 000367
- to stream Pmc, to step Checkpoint: 000B23
Links to Exploration step
PMC:2612304Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Evaluation of Live Attenuated Influenza A Virus H6 Vaccines in Mice and Ferrets<xref ref-type="fn" rid="fn3">▿</xref> </title><author><name sortKey="Chen, Zhongying" sort="Chen, Zhongying" uniqKey="Chen Z" first="Zhongying" last="Chen">Zhongying Chen</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Santos, Celia" sort="Santos, Celia" uniqKey="Santos C" first="Celia" last="Santos">Celia Santos</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Aspelund, Amy" sort="Aspelund, Amy" uniqKey="Aspelund A" first="Amy" last="Aspelund">Amy Aspelund</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Gillim Ross, Laura" sort="Gillim Ross, Laura" uniqKey="Gillim Ross L" first="Laura" last="Gillim-Ross">Laura Gillim-Ross</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Jin, Hong" sort="Jin, Hong" uniqKey="Jin H" first="Hong" last="Jin">Hong Jin</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Kemble, George" sort="Kemble, George" uniqKey="Kemble G" first="George" last="Kemble">George Kemble</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">18945773</idno><idno type="pmc">2612304</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2612304</idno><idno type="RBID">PMC:2612304</idno><idno type="doi">10.1128/JVI.01775-08</idno><date when="2008">2008</date><idno type="wicri:Area/Pmc/Corpus">000367</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000367</idno><idno type="wicri:Area/Pmc/Curation">000367</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000367</idno><idno type="wicri:Area/Pmc/Checkpoint">000B23</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000B23</idno><idno type="wicri:Area/Ncbi/Merge">000331</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Evaluation of Live Attenuated Influenza A Virus H6 Vaccines in Mice and Ferrets<xref ref-type="fn" rid="fn3">▿</xref> </title><author><name sortKey="Chen, Zhongying" sort="Chen, Zhongying" uniqKey="Chen Z" first="Zhongying" last="Chen">Zhongying Chen</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Santos, Celia" sort="Santos, Celia" uniqKey="Santos C" first="Celia" last="Santos">Celia Santos</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Aspelund, Amy" sort="Aspelund, Amy" uniqKey="Aspelund A" first="Amy" last="Aspelund">Amy Aspelund</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Gillim Ross, Laura" sort="Gillim Ross, Laura" uniqKey="Gillim Ross L" first="Laura" last="Gillim-Ross">Laura Gillim-Ross</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Jin, Hong" sort="Jin, Hong" uniqKey="Jin H" first="Hong" last="Jin">Hong Jin</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Kemble, George" sort="Kemble, George" uniqKey="Kemble G" first="George" last="Kemble">George Kemble</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">Journal of Virology</title><idno type="ISSN">0022-538X</idno><idno type="eISSN">1098-5514</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Avian influenza A virus A/teal/HK/W312/97 (H6N1) possesses seven gene segments that are highly homologous to those of highly pathogenic human influenza H5N1 viruses, suggesting that a W312-like H6N1 virus might have been involved in the generation of the A/HK/97 H5N1 viruses. The continuous circulation and reassortment of influenza H6 subtype viruses in birds highlight the need to develop an H6 vaccine to prevent potential influenza pandemics caused by the H6 viruses. Based on the serum antibody cross-reactivity data obtained from 14 different H6 viruses from Eurasian and North American lineages, A/duck/HK/182/77, A/teal/HK/W312/97, and A/mallard/Alberta/89/85 were selected to produce live attenuated H6 candidate vaccines. Each of the H6 vaccine strains is a 6:2 reassortant <italic>ca</italic> virus containing HA and NA gene segments from an H6 virus and the six internal gene segments from cold-adapted A/Ann Arbor/6/60 (AA <italic>ca</italic>), the master donor virus that is used to make live attenuated influenza virus FluMist (intranasal) vaccine. All three H6 vaccine candidates exhibited phenotypic properties of temperature sensitivity (<italic>ts</italic>), <italic>ca</italic>, and attenuation (<italic>att</italic>) conferred by the internal gene segments from AA <italic>ca</italic>. Intranasal administration of a single dose of the three H6 <italic>ca</italic> vaccine viruses induced neutralizing antibodies in mice and ferrets and fully protected mice and ferrets from homologous wild-type (wt) virus challenge. Among the three H6 vaccine candidates, the A/teal/HK/W312/97 <italic>ca</italic> virus provided the broadest cross-protection against challenge with three antigenically distinct H6 wt viruses. These data support the rationale for further evaluating the A/teal/HK/W312/97 <italic>ca</italic> vaccine in humans.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Virol</journal-id><journal-id journal-id-type="publisher-id">jvi</journal-id><journal-title>Journal of Virology</journal-title><issn pub-type="ppub">0022-538X</issn><issn pub-type="epub">1098-5514</issn><publisher><publisher-name>American Society for Microbiology (ASM)</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">18945773</article-id><article-id pub-id-type="pmc">2612304</article-id><article-id pub-id-type="publisher-id">1775-08</article-id><article-id pub-id-type="doi">10.1128/JVI.01775-08</article-id><article-categories><subj-group subj-group-type="heading"><subject>Vaccines and Antiviral Agents</subject></subj-group></article-categories><title-group><article-title>Evaluation of Live Attenuated Influenza A Virus H6 Vaccines in Mice and Ferrets<xref ref-type="fn" rid="fn3">▿</xref> </article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Zhongying</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="fn" rid="fn1">†</xref></contrib><contrib contrib-type="author"><name><surname>Santos</surname><given-names>Celia</given-names></name><xref ref-type="aff" rid="aff1">2</xref><xref ref-type="fn" rid="fn1">†</xref></contrib><contrib contrib-type="author"><name><surname>Aspelund</surname><given-names>Amy</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Gillim-Ross</surname><given-names>Laura</given-names></name><xref ref-type="aff" rid="aff1">2</xref><xref ref-type="fn" rid="fn2">‡</xref></contrib><contrib contrib-type="author"><name><surname>Jin</surname><given-names>Hong</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Kemble</surname><given-names>George</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Subbarao</surname><given-names>Kanta</given-names></name><xref ref-type="aff" rid="aff1">2</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="aff1">MedImmune, Mountain View, California 94043,<label>1</label> Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland 20892<label>2</label></aff><author-notes><fn id="cor1"><label>*</label><p>Corresponding author. Mailing address: Laboratory of Infectious Diseases, NIAID, NIH, Bldg. 33/Room 3E13C.1, 33 North Dr., MSC 3203, Bethesda, MD 20892. Phone: (301) 451-3839. Fax: (301) 480-4749. E-mail: <email>ksubbarao@niaid.nih.gov</email></p></fn><fn id="fn1"><label>†</label><p>Both authors contributed to the work equally.</p></fn><fn id="fn2"><label>‡</label><p>Present address: Colorado Department of Public Health and Environment, 8100 Lowry Blvd., Denver, CO 80230.</p></fn></author-notes><pub-date pub-type="ppub"><month>1</month><year>2009</year></pub-date><pub-date pub-type="epub"><day>22</day><month>10</month><year>2008</year></pub-date><volume>83</volume><issue>1</issue><fpage>65</fpage><lpage>72</lpage><history><date date-type="received"><day>22</day><month>8</month><year>2008</year></date><date date-type="accepted"><day>13</day><month>10</month><year>2008</year></date></history><permissions><copyright-statement>Copyright © 2009, American Society for Microbiology</copyright-statement></permissions><self-uri xlink:title="pdf" xlink:href="zjv00109000065.pdf"></self-uri><abstract><p>Avian influenza A virus A/teal/HK/W312/97 (H6N1) possesses seven gene segments that are highly homologous to those of highly pathogenic human influenza H5N1 viruses, suggesting that a W312-like H6N1 virus might have been involved in the generation of the A/HK/97 H5N1 viruses. The continuous circulation and reassortment of influenza H6 subtype viruses in birds highlight the need to develop an H6 vaccine to prevent potential influenza pandemics caused by the H6 viruses. Based on the serum antibody cross-reactivity data obtained from 14 different H6 viruses from Eurasian and North American lineages, A/duck/HK/182/77, A/teal/HK/W312/97, and A/mallard/Alberta/89/85 were selected to produce live attenuated H6 candidate vaccines. Each of the H6 vaccine strains is a 6:2 reassortant <italic>ca</italic> virus containing HA and NA gene segments from an H6 virus and the six internal gene segments from cold-adapted A/Ann Arbor/6/60 (AA <italic>ca</italic>), the master donor virus that is used to make live attenuated influenza virus FluMist (intranasal) vaccine. All three H6 vaccine candidates exhibited phenotypic properties of temperature sensitivity (<italic>ts</italic>), <italic>ca</italic>, and attenuation (<italic>att</italic>) conferred by the internal gene segments from AA <italic>ca</italic>. Intranasal administration of a single dose of the three H6 <italic>ca</italic> vaccine viruses induced neutralizing antibodies in mice and ferrets and fully protected mice and ferrets from homologous wild-type (wt) virus challenge. Among the three H6 vaccine candidates, the A/teal/HK/W312/97 <italic>ca</italic> virus provided the broadest cross-protection against challenge with three antigenically distinct H6 wt viruses. These data support the rationale for further evaluating the A/teal/HK/W312/97 <italic>ca</italic> vaccine in humans.</p></abstract></article-meta></front><floats-wrap><fig position="float" id="f1"><label>FIG. 1.</label><caption><p>Efficacy of H6 <italic>ca</italic> viruses in ferrets. Groups of three or four ferrets were inoculated i.n. with phosphate-buffered saline (mock), dk/HK/77 <italic>ca</italic>, tl/HK/97 <italic>ca</italic>, ma/Alb/85 <italic>ca</italic>, or H1N1 A/New Caledonia/20/99 (A/NC <italic>ca</italic>), and 32 days later, the animals were challenged with H6 wt viruses dk/HK/77, tl/HK/97, and ma/Alb/85. Three days postchallenge, virus titers in the lungs and NT tissues were determined by PFU (NT) or EID<sub>50</sub> (lungs) assay. Bars represent the means and standard errors of titers. The lower limit of detection is represented by the dotted line. *, <italic>P</italic> value of <0.05 compared to that for mock-immunized ferrets.</p></caption><graphic xlink:href="zjv0010913910001"></graphic></fig><fig position="float" id="f2"><label>FIG. 2.</label><caption><p>Ferret body weight change following H6 wt virus challenge. Groups of ferrets were mock vaccinated or vaccinated with dk/HK/77 <italic>ca</italic>, tl/HK/97 <italic>ca</italic>, or ma/Alb/85 <italic>ca</italic>. After 32 days, ferrets were challenged with homologous and heterologous H6 wt viruses dk/HK/77 (A), tl/HK/97 (B), and ma/Alb/85 (C). Body weight was measured each day from day 0 to day 3 after challenge and is represented as mean body weight loss or gain from the body weights of four ferrets at the time of challenge.</p></caption><graphic xlink:href="zjv0010913910002"></graphic></fig><fig position="float" id="f3"><label>FIG. 3.</label><caption><p>Efficacy of H6 <italic>ca</italic> viruses in mice. Groups of four mice were inoculated i.n. with either one dose (A) or two doses (B) of 10<sup>6</sup> TCID<sub>50</sub> of H6 <italic>ca</italic> viruses. Mice were challenged i.n. with homologous and heterologous H6 wt viruses 4 weeks after one dose or 4 weeks after two doses of H6 <italic>ca</italic> virus. Virus titers were determined for lungs and NT on day 4 postchallenge. Each bar represents the mean and standard error of titers for four mice. Statistical significance was determined using the nonparametric Mann-Whitney U test, and * indicates a <italic>P</italic> value of <0.05. The lower limit of detection is represented by the dotted lines.</p></caption><graphic xlink:href="zjv0010913910003"></graphic></fig><table-wrap position="float" id="t1"><label>TABLE 1.</label><caption><p>AI virus isolates of the H6 subtype included in this study</p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="1" rowspan="1" align="center" valign="bottom">Virus name</th><th colspan="1" rowspan="1" align="center" valign="bottom">Abbreviation</th><th colspan="1" rowspan="1" align="center" valign="bottom">Subtype</th><th colspan="1" rowspan="1" align="center" valign="bottom">Phylogenetic lineage<xref ref-type="table-fn" rid="t1fn1"><italic>a</italic></xref></th></tr></thead><tbody><tr><td colspan="1" rowspan="1" align="left" valign="top">A/duck/HK/182/77</td><td colspan="1" rowspan="1" align="left" valign="top">dk/HK/77</td><td colspan="1" rowspan="1" align="left" valign="top">H6N9</td><td colspan="1" rowspan="1" align="left" valign="top">Eurasian</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">A/teal/HK/W312/97</td><td colspan="1" rowspan="1" align="left" valign="top">tl/HK/97</td><td colspan="1" rowspan="1" align="left" valign="top">H6N1</td><td colspan="1" rowspan="1" align="left" valign="top">Eurasian</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">A/quail/HK/1721-30/99</td><td colspan="1" rowspan="1" align="left" valign="top">qu/HK/99</td><td colspan="1" rowspan="1" align="left" valign="top">H6N1</td><td colspan="1" rowspan="1" align="left" valign="top">Eurasian</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">A/mallard/Alberta/89/85</td><td colspan="1" rowspan="1" align="left" valign="top">ma/Alb/85</td><td colspan="1" rowspan="1" align="left" valign="top">H6N2</td><td colspan="1" rowspan="1" align="left" valign="top">North American</td></tr></tbody></table><table-wrap-foot><fn id="t1fn1"><label>a</label><p>Phylogenetic analysis based on HA amino acid sequence was generated using the neighbor joining method rooted on the AA H2 HA.</p></fn></table-wrap-foot></table-wrap><table-wrap position="float" id="t2"><label>TABLE 2.</label><caption><p>H6 <italic>ca</italic> viruses exhibit <italic>ts</italic> and <italic>ca</italic> phenotypes<xref ref-type="table-fn" rid="t2fn1"><italic>a</italic></xref></p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="1" rowspan="2" align="center" valign="middle">Virus</th><th colspan="5" rowspan="1" align="center" valign="bottom">Virus titer (log<sub>10</sub> TCID<sub>50</sub>/ml) at:
<hr></hr></th><th colspan="2" rowspan="1" align="center" valign="bottom">Phenotype
<hr></hr></th></tr><tr><th colspan="1" rowspan="1" align="center" valign="bottom">39°C</th><th colspan="1" rowspan="1" align="center" valign="bottom">33°C</th><th colspan="1" rowspan="1" align="center" valign="bottom">25°C</th><th colspan="1" rowspan="1" align="center" valign="bottom">Δ33/39°C</th><th colspan="1" rowspan="1" align="center" valign="bottom">Δ33/25°C</th><th colspan="1" rowspan="1" align="center" valign="bottom"><italic>ts</italic><xref ref-type="table-fn" rid="t2fn2"><italic>b</italic></xref></th><th colspan="1" rowspan="1" align="center" valign="bottom"><italic>ca</italic><xref ref-type="table-fn" rid="t2fn3"><italic>c</italic></xref></th></tr></thead><tbody><tr><td colspan="1" rowspan="1" align="left" valign="top">dk/HK/77</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> wt</td><td colspan="1" rowspan="1" align="char" char="." valign="top">8.5</td><td colspan="1" rowspan="1" align="char" char="." valign="top">8.3</td><td colspan="1" rowspan="1" align="char" char="." valign="top">4.0</td><td colspan="1" rowspan="1" align="char" char="." valign="top">−0.2</td><td colspan="1" rowspan="1" align="char" char="." valign="top">4.3</td><td colspan="1" rowspan="1" align="center" valign="top">−</td><td colspan="1" rowspan="1" align="center" valign="top">−</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> <italic>ca</italic></td><td colspan="1" rowspan="1" align="char" char="." valign="top">4.2</td><td colspan="1" rowspan="1" align="char" char="." valign="top">8.1</td><td colspan="1" rowspan="1" align="char" char="." valign="top">6.3</td><td colspan="1" rowspan="1" align="char" char="." valign="top">3.9</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1.8</td><td colspan="1" rowspan="1" align="center" valign="top">+</td><td colspan="1" rowspan="1" align="center" valign="top">+</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">tl/HK/97</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> wt</td><td colspan="1" rowspan="1" align="char" char="." valign="top">9.0</td><td colspan="1" rowspan="1" align="char" char="." valign="top">8.7</td><td colspan="1" rowspan="1" align="char" char="." valign="top">4.2</td><td colspan="1" rowspan="1" align="char" char="." valign="top">−0.3</td><td colspan="1" rowspan="1" align="char" char="." valign="top">4.5</td><td colspan="1" rowspan="1" align="center" valign="top">−</td><td colspan="1" rowspan="1" align="center" valign="top">−</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> <italic>ca</italic></td><td colspan="1" rowspan="1" align="char" char="." valign="top">5.2</td><td colspan="1" rowspan="1" align="char" char="." valign="top">8.7</td><td colspan="1" rowspan="1" align="char" char="." valign="top">8.2</td><td colspan="1" rowspan="1" align="char" char="." valign="top">3.5</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.5</td><td colspan="1" rowspan="1" align="center" valign="top">+</td><td colspan="1" rowspan="1" align="center" valign="top">+</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">ma/Alb/85</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> wt</td><td colspan="1" rowspan="1" align="char" char="." valign="top">8.5</td><td colspan="1" rowspan="1" align="char" char="." valign="top">8.0</td><td colspan="1" rowspan="1" align="char" char="." valign="top">4.2</td><td colspan="1" rowspan="1" align="char" char="." valign="top">−0.5</td><td colspan="1" rowspan="1" align="char" char="." valign="top">3.8</td><td colspan="1" rowspan="1" align="center" valign="top">−</td><td colspan="1" rowspan="1" align="center" valign="top">−</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> <italic>ca</italic></td><td colspan="1" rowspan="1" align="char" char="." valign="top">5.0</td><td colspan="1" rowspan="1" align="char" char="." valign="top">8.2</td><td colspan="1" rowspan="1" align="char" char="." valign="top">7.3</td><td colspan="1" rowspan="1" align="char" char="." valign="top">3.2</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.9</td><td colspan="1" rowspan="1" align="center" valign="top">+</td><td colspan="1" rowspan="1" align="center" valign="top">+</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">AA <italic>ca</italic></td><td colspan="1" rowspan="1" align="char" char="." valign="top">5.2</td><td colspan="1" rowspan="1" align="char" char="." valign="top">9.3</td><td colspan="1" rowspan="1" align="char" char="." valign="top">8.2</td><td colspan="1" rowspan="1" align="char" char="." valign="top">4.1</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1.1</td><td colspan="1" rowspan="1" align="center" valign="top">+</td><td colspan="1" rowspan="1" align="center" valign="top">+</td></tr></tbody></table><table-wrap-foot><fn id="t2fn1"><label>a</label><p>CEK cells were inoculated with H6 wt and <italic>ca</italic> viruses or AA <italic>ca</italic> and were incubated at 39, 33, and 25°C. After incubation for 6 days at 39°C and 33°C or 10 days at 25°C to reach peak titers, cells were examined for CPE, and virus titers (TCID<sub>50</sub>) at each temperature were determined.</p></fn><fn id="t2fn2"><label>b</label><p><italic>ts</italic>, difference between the mean TCID<sub>50</sub> at 33°C and 39°C of ≥100-fold.</p></fn><fn id="t2fn3"><label>c</label><p><italic>ca</italic>, difference between the mean TCID<sub>50</sub> at 33°C and 25°C of ≤100-fold.</p></fn></table-wrap-foot></table-wrap><table-wrap position="float" id="t3"><label>TABLE 3.</label><caption><p>Replication of wt and <italic>ca</italic> H6 viruses in ferrets<xref ref-type="table-fn" rid="t3fn1"><italic>a</italic></xref></p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="1" rowspan="3" align="center" valign="middle">Virus</th><th colspan="1" rowspan="3" align="center" valign="middle">dpi</th><th colspan="4" rowspan="1" align="center" valign="bottom">Virus titer in:
<hr></hr></th></tr><tr><th colspan="2" rowspan="1" align="center" valign="bottom">Lungs (log<sub>10</sub> EID<sub>50</sub>/g ± SE)
<hr></hr></th><th colspan="2" rowspan="1" align="center" valign="bottom">NT (log<sub>10</sub> PFU/g ± SE)
<hr></hr></th></tr><tr><th colspan="1" rowspan="1" align="center" valign="bottom">wt</th><th colspan="1" rowspan="1" align="center" valign="bottom"><italic>ca</italic></th><th colspan="1" rowspan="1" align="center" valign="bottom">wt</th><th colspan="1" rowspan="1" align="center" valign="bottom"><italic>ca</italic></th></tr></thead><tbody><tr><td colspan="1" rowspan="1" align="left" valign="top">dk/HK/77</td><td colspan="1" rowspan="1" align="char" char="." valign="top">3</td><td colspan="1" rowspan="1" align="center" valign="top">7.0 ± 0.5</td><td colspan="1" rowspan="1" align="char" char="." valign="top">≤1.5<xref ref-type="table-fn" rid="t3fn2"><italic>b</italic></xref></td><td colspan="1" rowspan="1" align="center" valign="top">5.4 ± 0.1</td><td colspan="1" rowspan="1" align="center" valign="top">2.5 ± 0.2</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top">5</td><td colspan="1" rowspan="1" align="center" valign="top">6.0 ± 0.5</td><td colspan="1" rowspan="1" align="char" char="." valign="top">≤1.5</td><td colspan="1" rowspan="1" align="center" valign="top">6.1 ± 0.0</td><td colspan="1" rowspan="1" align="center" valign="top">2.6 ± 0.6</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">tl/HK/97</td><td colspan="1" rowspan="1" align="char" char="." valign="top">3</td><td colspan="1" rowspan="1" align="center" valign="top">6.3 ± 0.2</td><td colspan="1" rowspan="1" align="char" char="." valign="top">≤1.5</td><td colspan="1" rowspan="1" align="center" valign="top">6.0 ± 0.3</td><td colspan="1" rowspan="1" align="center" valign="top">2.1 ± 0.0</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top">5</td><td colspan="1" rowspan="1" align="center" valign="top">7.2 ± 0.3</td><td colspan="1" rowspan="1" align="char" char="." valign="top">≤1.5</td><td colspan="1" rowspan="1" align="center" valign="top">5.4 ± 0.0</td><td colspan="1" rowspan="1" align="center" valign="top">2.4 ± 0.3</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">ma/Alb/85</td><td colspan="1" rowspan="1" align="char" char="." valign="top">3</td><td colspan="1" rowspan="1" align="center" valign="top">6.5 ± 0.0</td><td colspan="1" rowspan="1" align="char" char="." valign="top">≤1.5</td><td colspan="1" rowspan="1" align="center" valign="top">3.9 ± 0.0</td><td colspan="1" rowspan="1" align="center" valign="top">2.0 ± 0.0</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top">5</td><td colspan="1" rowspan="1" align="center" valign="top">5.8<xref ref-type="table-fn" rid="t3fn3"><italic>c</italic></xref></td><td colspan="1" rowspan="1" align="center" valign="top">NT<xref ref-type="table-fn" rid="t3fn4"><italic>d</italic></xref></td><td colspan="1" rowspan="1" align="center" valign="top">2.1<xref ref-type="table-fn" rid="t3fn3"><italic>c</italic></xref></td><td colspan="1" rowspan="1" align="center" valign="top">NT<xref ref-type="table-fn" rid="t3fn4"><italic>d</italic></xref></td></tr></tbody></table><table-wrap-foot><fn id="t3fn1"><label>a</label><p>Groups of four ferrets were inoculated i.n. with 10<sup>7.0</sup> PFU (0.25 ml per nostril) of the indicated H6 wt and <italic>ca</italic> viruses. At 3 and 5 dpi, NT and lungs of two ferrets were collected and virus titers were determined. Each data set represents the mean for two ferrets.</p></fn><fn id="t3fn2"><label>b</label><p>Below the limit of detection.</p></fn><fn id="t3fn3"><label>c</label><p>Data from one ferret.</p></fn><fn id="t3fn4"><label>d</label><p>NT, not tested.</p></fn></table-wrap-foot></table-wrap><table-wrap position="float" id="t4"><label>TABLE 4.</label><caption><p>Immunogenicity of H6 <italic>ca</italic> viruses after a single dose of vaccine in ferrets<xref ref-type="table-fn" rid="t4fn1"><italic>a</italic></xref></p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="1" rowspan="3" align="center" valign="middle">Test antigen used in serological assay</th><th colspan="6" rowspan="1" align="center" valign="bottom">Geometric mean titer of serum antibody in ferrets immunized with<xref ref-type="table-fn" rid="t4fn2"><italic>b</italic></xref>:
<hr></hr></th></tr><tr><th colspan="2" rowspan="1" align="center" valign="bottom">dk/HK/77 <italic>ca</italic><hr></hr></th><th colspan="2" rowspan="1" align="center" valign="bottom">tl/HK/97 <italic>ca</italic><hr></hr></th><th colspan="2" rowspan="1" align="center" valign="bottom">ma/Alb/85 <italic>ca</italic><hr></hr></th></tr><tr><th colspan="1" rowspan="1" align="center" valign="bottom">NtAb</th><th colspan="1" rowspan="1" align="center" valign="bottom">HAI</th><th colspan="1" rowspan="1" align="center" valign="bottom">NtAb</th><th colspan="1" rowspan="1" align="center" valign="bottom">HAI</th><th colspan="1" rowspan="1" align="center" valign="bottom">NtAb</th><th colspan="1" rowspan="1" align="center" valign="bottom">HAI</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" align="left" valign="top">dk/HK/77 <italic>ca</italic></td><td colspan="1" rowspan="1" align="char" char="." valign="top"><underline><underline>160</underline></underline></td><td colspan="1" rowspan="1" align="char" char="." valign="top"><underline><underline>215</underline></underline></td><td colspan="1" rowspan="1" align="char" char="." valign="top">48</td><td colspan="1" rowspan="1" align="char" char="." valign="top">27</td><td colspan="1" rowspan="1" align="char" char="." valign="top">25</td><td colspan="1" rowspan="1" align="char" char="." valign="top">4</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">tl/HK/97 <italic>ca</italic></td><td colspan="1" rowspan="1" align="char" char="." valign="top">57</td><td colspan="1" rowspan="1" align="char" char="." valign="top">16</td><td colspan="1" rowspan="1" align="char" char="." valign="top"><underline><underline>269</underline></underline></td><td colspan="1" rowspan="1" align="char" char="." valign="top"><underline><underline>128</underline></underline></td><td colspan="1" rowspan="1" align="char" char="." valign="top">20</td><td colspan="1" rowspan="1" align="char" char="." valign="top">4</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">ma/Alb/85 <italic>ca</italic></td><td colspan="1" rowspan="1" align="char" char="." valign="top">24</td><td colspan="1" rowspan="1" align="char" char="." valign="top">4</td><td colspan="1" rowspan="1" align="char" char="." valign="top">34</td><td colspan="1" rowspan="1" align="char" char="." valign="top">4</td><td colspan="1" rowspan="1" align="char" char="." valign="top"><underline><underline>190</underline></underline></td><td colspan="1" rowspan="1" align="char" char="." valign="top"><underline><underline>861</underline></underline></td></tr></tbody></table><table-wrap-foot><fn id="t4fn1"><label>a</label><p>Groups of four ferrets were inoculated i.n. with 10<sup>7.0</sup> PFU of the indicated H6 <italic>ca</italic> viruses. Serum was collected 14 days after immunization.</p></fn><fn id="t4fn2"><label>b</label><p>NtAb and HAI titers were determined by microneutralization assay and HAI assay using horse erythrocytes. Antibody titers against homologous viruses are underlined. An undetectable serum NtAb titer was assigned a value of 20 and an undetectable HAI antibody titer was assigned a value of 4.</p></fn></table-wrap-foot></table-wrap><table-wrap position="float" id="t5"><label>TABLE 5.</label><caption><p>Immunogenicity of a single dose and of two doses of H6 <italic>ca</italic> viruses in mice<xref ref-type="table-fn" rid="t5fn1"><italic>a</italic></xref></p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="1" rowspan="3" align="center" valign="middle">Test antigen used in NtAb assay</th><th colspan="6" rowspan="1" align="center" valign="bottom">Geometric mean titer of serum NtAb in mice immunized with<xref ref-type="table-fn" rid="t5fn2"><italic>b</italic></xref>:
<hr></hr></th></tr><tr><th colspan="2" rowspan="1" align="center" valign="bottom">dk/HK/77 <italic>ca</italic><hr></hr></th><th colspan="2" rowspan="1" align="center" valign="bottom">ma/Alb/85 <italic>ca</italic><hr></hr></th><th colspan="2" rowspan="1" align="center" valign="bottom">tl/HK/97 <italic>ca</italic><hr></hr></th></tr><tr><th colspan="1" rowspan="1" align="center" valign="bottom">1 Dose</th><th colspan="1" rowspan="1" align="center" valign="bottom">2 Doses</th><th colspan="1" rowspan="1" align="center" valign="bottom">1 Dose</th><th colspan="1" rowspan="1" align="center" valign="bottom">2 Doses</th><th colspan="1" rowspan="1" align="center" valign="bottom">1 Dose</th><th colspan="1" rowspan="1" align="center" valign="bottom">2 Doses</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" align="left" valign="top">dk/HK/77 wt</td><td colspan="1" rowspan="1" align="char" char="." valign="top"><underline><underline>214</underline></underline></td><td colspan="1" rowspan="1" align="char" char="." valign="top"><underline><underline>528</underline></underline></td><td colspan="1" rowspan="1" align="char" char="." valign="top">44</td><td colspan="1" rowspan="1" align="char" char="." valign="top">29</td><td colspan="1" rowspan="1" align="char" char="." valign="top">27</td><td colspan="1" rowspan="1" align="char" char="." valign="top">85</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">ma/Alb/85 wt</td><td colspan="1" rowspan="1" align="char" char="." valign="top">10<xref ref-type="table-fn" rid="t5fn3"><italic>c</italic></xref></td><td colspan="1" rowspan="1" align="char" char="." valign="top">10</td><td colspan="1" rowspan="1" align="char" char="." valign="top"><underline><underline>314</underline></underline></td><td colspan="1" rowspan="1" align="char" char="." valign="top"><underline><underline>3,044</underline></underline></td><td colspan="1" rowspan="1" align="char" char="." valign="top">10</td><td colspan="1" rowspan="1" align="char" char="." valign="top">15</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">tl/HK/97 wt</td><td colspan="1" rowspan="1" align="char" char="." valign="top">10</td><td colspan="1" rowspan="1" align="char" char="." valign="top">10</td><td colspan="1" rowspan="1" align="char" char="." valign="top">10</td><td colspan="1" rowspan="1" align="char" char="." valign="top">10</td><td colspan="1" rowspan="1" align="char" char="." valign="top"><underline><underline>94</underline></underline></td><td colspan="1" rowspan="1" align="char" char="." valign="top"><underline><underline>543</underline></underline></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">qu/HK/99 wt</td><td colspan="1" rowspan="1" align="char" char="." valign="top">10</td><td colspan="1" rowspan="1" align="char" char="." valign="top">10</td><td colspan="1" rowspan="1" align="char" char="." valign="top">10</td><td colspan="1" rowspan="1" align="char" char="." valign="top">10</td><td colspan="1" rowspan="1" align="char" char="." valign="top">86</td><td colspan="1" rowspan="1" align="char" char="." valign="top">388</td></tr></tbody></table><table-wrap-foot><fn id="t5fn1"><label>a</label><p>Groups of eight mice were inoculated i.n. with 10<sup>6</sup> TCID<sub>50</sub> of H6 <italic>ca</italic> viruses. NtAb titers were determined for sera collected 4 weeks after the first dose and 2 weeks after the second dose of vaccination by microneutralization assay in MDCK cells.</p></fn><fn id="t5fn2"><label>b</label><p>Antibody titers against homologous viruses are underlined.</p></fn><fn id="t5fn3"><label>c</label><p>Undetectable titer was assigned as 10.</p></fn></table-wrap-foot></table-wrap></floats-wrap></pmc><affiliations><list></list><tree><noCountry><name sortKey="Aspelund, Amy" sort="Aspelund, Amy" uniqKey="Aspelund A" first="Amy" last="Aspelund">Amy Aspelund</name><name sortKey="Chen, Zhongying" sort="Chen, Zhongying" uniqKey="Chen Z" first="Zhongying" last="Chen">Zhongying Chen</name><name sortKey="Gillim Ross, Laura" sort="Gillim Ross, Laura" uniqKey="Gillim Ross L" first="Laura" last="Gillim-Ross">Laura Gillim-Ross</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="Santos, Celia" sort="Santos, Celia" uniqKey="Santos C" first="Celia" last="Santos">Celia Santos</name><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/H2N2V1/Data/Ncbi/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000331 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd -nk 000331 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= H2N2V1
|flux= Ncbi
|étape= Merge
|type= RBID
|clé= PMC:2612304
|texte= Evaluation of Live Attenuated Influenza A Virus H6 Vaccines in Mice and Ferrets▿
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/RBID.i -Sk "pubmed:18945773" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd \
| NlmPubMed2Wicri -a H2N2V1
| This area was generated with Dilib version V0.6.33. |  |