A live attenuated H7N3 influenza virus vaccine is well tolerated and immunogenic in a Phase I trial in healthy adults
Identifieur interne : 000047 ( PascalFrancis/Curation ); précédent : 000046; suivant : 000048A live attenuated H7N3 influenza virus vaccine is well tolerated and immunogenic in a Phase I trial in healthy adults
Auteurs : Kawsar R. Talaat [États-Unis] ; Ruth A. Karron [États-Unis] ; Karen A. Callahan [États-Unis] ; Catherine J. Luke [États-Unis] ; Susan C. Dilorenzo [États-Unis] ; Grace L. Chen [États-Unis] ; Elaine W. Lamirande [États-Unis] ; HONG JIN [États-Unis] ; Kathy L. Coelingh [États-Unis] ; Brian R. Murphy [États-Unis] ; George Kemble [États-Unis] ; Kanta Subbarao [États-Unis]Source :
- Vaccine [ 0264-410X ] ; 2009.
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- Pascal (Inist)
- Wicri :
- topic : Vaccin.
English descriptors
- KwdEn :
Abstract
Background: Live attenuated influenza vaccines (LAIVs) are being developed and tested against a variety of influenza viruses with pandemic potential. We describe the results of an open-label Phase I trial of a live attenuated H7N3 virus vaccine. Methods and findings: The H7N3 BC 2004/AA ca virus is a live attenuated, cold-adapted, temperature-sensitive influenza virus derived by reverse genetics from the wild-type low pathogenicity avian influenza virus A/chicken/British Columbia/CN-6/2004 (H7N3) and the A/AA/6/60 ca (H2N2) virus that is the Master Donor Virus of the live, intranasal seasonal influenza vaccine. We evaluated the safety, infectivity, and immunogenicity of two doses of 107.5 TCID50 of the vaccine administered by nasal spray 5 weeks apart to normal healthy seronegative adult volunteers in an inpatient isolation unit. The subjects were followed for 2 months after one dose of vaccine or for 4 weeks after the second dose. Twenty-one subjects received the first dose of the vaccine, and 17 subjects received two doses. The vaccine was generally well tolerated. No serious adverse events occurred during the trial. The vaccine was highly restricted in replication: 6 (29%) subjects had virus recoverable by culture or by real-time reverse transcription polymerase chain reaction (rRT-PCR) after the first dose. Replication of vaccine virus was not detected following the second dose. Despite the restricted replication of the vaccine, 90% of the subjects developed an antibody response as measured by any assay: 62% by hemagglutination inhibition assay, 48% by microneutralization assay, 48% by ELISA for H7 HA-specific serum IgG or 71% by ELISA for H7 HA-specific serum IgA, after either one or two doses. Following the first dose, vaccine-specific IgG secreting cells as measured by ELISPOT increased from a mean of 0.1 to 41.6/106 PBMCs; vaccine-specific IgA secreting cells increased from 2 to 16.4/106 PBMCs. The antibody secreting cell response after the second dose was less vigorous, which is consistent with the observed low replication of vaccine virus after the second dose and consequent lower antigenic stimulation. Conclusion: The live attenuated H7N3 vaccine was generally well tolerated but was highly restricted in replication in healthy seronegative adults. Despite the restricted replication, the vaccine was immunogenic, with serum IgA being the most sensitive measure of immunogenicity. Further development of this vaccine is warranted (ClinicalTrials.gov Identifier: NCT00516035).
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">A live attenuated H7N3 influenza virus vaccine is well tolerated and immunogenic in a Phase I trial in healthy adults</title><author><name sortKey="Talaat, Kawsar R" sort="Talaat, Kawsar R" uniqKey="Talaat K" first="Kawsar R." last="Talaat">Kawsar R. Talaat</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health</s1><s2>Baltimore, MD 21205</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Karron, Ruth A" sort="Karron, Ruth A" uniqKey="Karron R" first="Ruth A." last="Karron">Ruth A. 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Chen</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Laboratory of Infectious Diseases, National Institute for Allergy and Infectious Diseases, National Institutes of Health</s1><s2>Bethesda, MD 20892</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Lamirande, Elaine W" sort="Lamirande, Elaine W" uniqKey="Lamirande E" first="Elaine W." last="Lamirande">Elaine W. Lamirande</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Laboratory of Infectious Diseases, National Institute for Allergy and Infectious Diseases, National Institutes of Health</s1><s2>Bethesda, MD 20892</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Hong Jin" sort="Hong Jin" uniqKey="Hong Jin" last="Hong Jin">HONG JIN</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Medlmmune</s1><s2>Mountain View, CA 94043</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Coelingh, Kathy L" sort="Coelingh, Kathy L" uniqKey="Coelingh K" first="Kathy L." last="Coelingh">Kathy L. Coelingh</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Medlmmune</s1><s2>Mountain View, CA 94043</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Murphy, Brian R" sort="Murphy, Brian R" uniqKey="Murphy B" first="Brian R." last="Murphy">Brian R. Murphy</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Laboratory of Infectious Diseases, National Institute for Allergy and Infectious Diseases, National Institutes of Health</s1><s2>Bethesda, MD 20892</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Kemble, George" sort="Kemble, George" uniqKey="Kemble G" first="George" last="Kemble">George Kemble</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Medlmmune</s1><s2>Mountain View, CA 94043</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Laboratory of Infectious Diseases, National Institute for Allergy and Infectious Diseases, National Institutes of Health</s1><s2>Bethesda, MD 20892</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">09-0295897</idno><date when="2009">2009</date><idno type="stanalyst">PASCAL 09-0295897 INIST</idno><idno type="RBID">Pascal:09-0295897</idno><idno type="wicri:Area/PascalFrancis/Corpus">000027</idno><idno type="wicri:Area/PascalFrancis/Curation">000047</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">A live attenuated H7N3 influenza virus vaccine is well tolerated and immunogenic in a Phase I trial in healthy adults</title><author><name sortKey="Talaat, Kawsar R" sort="Talaat, Kawsar R" uniqKey="Talaat K" first="Kawsar R." last="Talaat">Kawsar R. Talaat</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health</s1><s2>Baltimore, MD 21205</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Karron, Ruth A" sort="Karron, Ruth A" uniqKey="Karron R" first="Ruth A." last="Karron">Ruth A. Karron</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health</s1><s2>Baltimore, MD 21205</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Callahan, Karen A" sort="Callahan, Karen A" uniqKey="Callahan K" first="Karen A." last="Callahan">Karen A. Callahan</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health</s1><s2>Baltimore, MD 21205</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Luke, Catherine J" sort="Luke, Catherine J" uniqKey="Luke C" first="Catherine J." last="Luke">Catherine J. Luke</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Laboratory of Infectious Diseases, National Institute for Allergy and Infectious Diseases, National Institutes of Health</s1><s2>Bethesda, MD 20892</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Dilorenzo, Susan C" sort="Dilorenzo, Susan C" uniqKey="Dilorenzo S" first="Susan C." last="Dilorenzo">Susan C. Dilorenzo</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health</s1><s2>Baltimore, MD 21205</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Chen, Grace L" sort="Chen, Grace L" uniqKey="Chen G" first="Grace L." last="Chen">Grace L. Chen</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Laboratory of Infectious Diseases, National Institute for Allergy and Infectious Diseases, National Institutes of Health</s1><s2>Bethesda, MD 20892</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Lamirande, Elaine W" sort="Lamirande, Elaine W" uniqKey="Lamirande E" first="Elaine W." last="Lamirande">Elaine W. Lamirande</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Laboratory of Infectious Diseases, National Institute for Allergy and Infectious Diseases, National Institutes of Health</s1><s2>Bethesda, MD 20892</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Hong Jin" sort="Hong Jin" uniqKey="Hong Jin" last="Hong Jin">HONG JIN</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Medlmmune</s1><s2>Mountain View, CA 94043</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Coelingh, Kathy L" sort="Coelingh, Kathy L" uniqKey="Coelingh K" first="Kathy L." last="Coelingh">Kathy L. Coelingh</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Medlmmune</s1><s2>Mountain View, CA 94043</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Murphy, Brian R" sort="Murphy, Brian R" uniqKey="Murphy B" first="Brian R." last="Murphy">Brian R. Murphy</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Laboratory of Infectious Diseases, National Institute for Allergy and Infectious Diseases, National Institutes of Health</s1><s2>Bethesda, MD 20892</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Kemble, George" sort="Kemble, George" uniqKey="Kemble G" first="George" last="Kemble">George Kemble</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Medlmmune</s1><s2>Mountain View, CA 94043</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Laboratory of Infectious Diseases, National Institute for Allergy and Infectious Diseases, National Institutes of Health</s1><s2>Bethesda, MD 20892</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author></analytic><series><title level="j" type="main">Vaccine</title><title level="j" type="abbreviated">Vaccine</title><idno type="ISSN">0264-410X</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Vaccine</title><title level="j" type="abbreviated">Vaccine</title><idno type="ISSN">0264-410X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Attenuated strain</term><term>Aves</term><term>Immunogenicity</term><term>Influenza</term><term>Influenza A virus</term><term>Phase I trial</term><term>Vaccine</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Virus grippal A</term><term>Aves</term><term>Souche atténuée</term><term>Vaccin</term><term>Immunogénicité</term><term>Essai clinique phase I</term><term>Grippe</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Vaccin</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Background: Live attenuated influenza vaccines (LAIVs) are being developed and tested against a variety of influenza viruses with pandemic potential. We describe the results of an open-label Phase I trial of a live attenuated H7N3 virus vaccine. Methods and findings: The H7N3 BC 2004/AA ca virus is a live attenuated, cold-adapted, temperature-sensitive influenza virus derived by reverse genetics from the wild-type low pathogenicity avian influenza virus A/chicken/British Columbia/CN-6/2004 (H7N3) and the A/AA/6/60 ca (H2N2) virus that is the Master Donor Virus of the live, intranasal seasonal influenza vaccine. We evaluated the safety, infectivity, and immunogenicity of two doses of 10<sup>7.5</sup> TCID<sub>50</sub> of the vaccine administered by nasal spray 5 weeks apart to normal healthy seronegative adult volunteers in an inpatient isolation unit. The subjects were followed for 2 months after one dose of vaccine or for 4 weeks after the second dose. Twenty-one subjects received the first dose of the vaccine, and 17 subjects received two doses. The vaccine was generally well tolerated. No serious adverse events occurred during the trial. The vaccine was highly restricted in replication: 6 (29%) subjects had virus recoverable by culture or by real-time reverse transcription polymerase chain reaction (rRT-PCR) after the first dose. Replication of vaccine virus was not detected following the second dose. Despite the restricted replication of the vaccine, 90% of the subjects developed an antibody response as measured by any assay: 62% by hemagglutination inhibition assay, 48% by microneutralization assay, 48% by ELISA for H7 HA-specific serum IgG or 71% by ELISA for H7 HA-specific serum IgA, after either one or two doses. Following the first dose, vaccine-specific IgG secreting cells as measured by ELISPOT increased from a mean of 0.1 to 41.6/10<sup>6</sup> PBMCs; vaccine-specific IgA secreting cells increased from 2 to 16.4/10<sup>6</sup> PBMCs. The antibody secreting cell response after the second dose was less vigorous, which is consistent with the observed low replication of vaccine virus after the second dose and consequent lower antigenic stimulation. Conclusion: The live attenuated H7N3 vaccine was generally well tolerated but was highly restricted in replication in healthy seronegative adults. Despite the restricted replication, the vaccine was immunogenic, with serum IgA being the most sensitive measure of immunogenicity. Further development of this vaccine is warranted (ClinicalTrials.gov Identifier: NCT00516035).</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0264-410X</s0></fA01><fA02 i1="01"><s0>VACCDE</s0></fA02><fA03 i2="1"><s0>Vaccine</s0></fA03><fA05><s2>27</s2></fA05><fA06><s2>28</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>A live attenuated H7N3 influenza virus vaccine is well tolerated and immunogenic in a Phase I trial in healthy adults</s1></fA08><fA11 i1="01" i2="1"><s1>TALAAT (Kawsar R.)</s1></fA11><fA11 i1="02" i2="1"><s1>KARRON (Ruth A.)</s1></fA11><fA11 i1="03" i2="1"><s1>CALLAHAN (Karen A.)</s1></fA11><fA11 i1="04" i2="1"><s1>LUKE (Catherine J.)</s1></fA11><fA11 i1="05" i2="1"><s1>DILORENZO (Susan C.)</s1></fA11><fA11 i1="06" i2="1"><s1>CHEN (Grace L.)</s1></fA11><fA11 i1="07" i2="1"><s1>LAMIRANDE (Elaine W.)</s1></fA11><fA11 i1="08" i2="1"><s1>HONG JIN</s1></fA11><fA11 i1="09" i2="1"><s1>COELINGH (Kathy L.)</s1></fA11><fA11 i1="10" i2="1"><s1>MURPHY (Brian R.)</s1></fA11><fA11 i1="11" i2="1"><s1>KEMBLE (George)</s1></fA11><fA11 i1="12" i2="1"><s1>SUBBARAO (Kanta)</s1></fA11><fA14 i1="01"><s1>Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health</s1><s2>Baltimore, MD 21205</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ></fA14><fA14 i1="02"><s1>Laboratory of Infectious Diseases, National Institute for Allergy and Infectious Diseases, National Institutes of Health</s1><s2>Bethesda, MD 20892</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></fA14><fA14 i1="03"><s1>Medlmmune</s1><s2>Mountain View, CA 94043</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ></fA14><fA20><s1>3744-3753</s1></fA20><fA21><s1>2009</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>20289</s2><s5>354000188373450100</s5></fA43><fA44><s0>0000</s0><s1>© 2009 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>63 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>09-0295897</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Vaccine</s0></fA64><fA66 i1="01"><s0>GBR</s0></fA66><fC01 i1="01" l="ENG"><s0>Background: Live attenuated influenza vaccines (LAIVs) are being developed and tested against a variety of influenza viruses with pandemic potential. We describe the results of an open-label Phase I trial of a live attenuated H7N3 virus vaccine. Methods and findings: The H7N3 BC 2004/AA ca virus is a live attenuated, cold-adapted, temperature-sensitive influenza virus derived by reverse genetics from the wild-type low pathogenicity avian influenza virus A/chicken/British Columbia/CN-6/2004 (H7N3) and the A/AA/6/60 ca (H2N2) virus that is the Master Donor Virus of the live, intranasal seasonal influenza vaccine. We evaluated the safety, infectivity, and immunogenicity of two doses of 10<sup>7.5</sup> TCID<sub>50</sub> of the vaccine administered by nasal spray 5 weeks apart to normal healthy seronegative adult volunteers in an inpatient isolation unit. The subjects were followed for 2 months after one dose of vaccine or for 4 weeks after the second dose. Twenty-one subjects received the first dose of the vaccine, and 17 subjects received two doses. The vaccine was generally well tolerated. No serious adverse events occurred during the trial. The vaccine was highly restricted in replication: 6 (29%) subjects had virus recoverable by culture or by real-time reverse transcription polymerase chain reaction (rRT-PCR) after the first dose. Replication of vaccine virus was not detected following the second dose. Despite the restricted replication of the vaccine, 90% of the subjects developed an antibody response as measured by any assay: 62% by hemagglutination inhibition assay, 48% by microneutralization assay, 48% by ELISA for H7 HA-specific serum IgG or 71% by ELISA for H7 HA-specific serum IgA, after either one or two doses. Following the first dose, vaccine-specific IgG secreting cells as measured by ELISPOT increased from a mean of 0.1 to 41.6/10<sup>6</sup> PBMCs; vaccine-specific IgA secreting cells increased from 2 to 16.4/10<sup>6</sup> PBMCs. The antibody secreting cell response after the second dose was less vigorous, which is consistent with the observed low replication of vaccine virus after the second dose and consequent lower antigenic stimulation. Conclusion: The live attenuated H7N3 vaccine was generally well tolerated but was highly restricted in replication in healthy seronegative adults. Despite the restricted replication, the vaccine was immunogenic, with serum IgA being the most sensitive measure of immunogenicity. Further development of this vaccine is warranted (ClinicalTrials.gov Identifier: NCT00516035).</s0></fC01><fC02 i1="01" i2="X"><s0>002A05F04</s0></fC02><fC02 i1="02" i2="X"><s0>002A05C10</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Virus grippal A</s0><s2>NW</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Influenza A virus</s0><s2>NW</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Influenza A virus</s0><s2>NW</s2><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Aves</s0><s2>NS</s2><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Aves</s0><s2>NS</s2><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Aves</s0><s2>NS</s2><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Souche atténuée</s0><s5>05</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Attenuated strain</s0><s5>05</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Cepa atenuada</s0><s5>05</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Vaccin</s0><s5>06</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Vaccine</s0><s5>06</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Vacuna</s0><s5>06</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Immunogénicité</s0><s5>07</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Immunogenicity</s0><s5>07</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Inmunogenicidad</s0><s5>07</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>Essai clinique phase I</s0><s5>08</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>Phase I trial</s0><s5>08</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>Ensayo clínico fase I</s0><s5>08</s5></fC03><fC03 i1="07" i2="X" l="FRE"><s0>Grippe</s0><s5>14</s5></fC03><fC03 i1="07" i2="X" l="ENG"><s0>Influenza</s0><s5>14</s5></fC03><fC03 i1="07" i2="X" l="SPA"><s0>Gripe</s0><s5>14</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Influenzavirus A</s0><s2>NW</s2></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Influenzavirus A</s0><s2>NW</s2></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Influenzavirus A</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Orthomyxoviridae</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Orthomyxoviridae</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Orthomyxoviridae</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Vertebrata</s0><s2>NS</s2></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Vertebrata</s0><s2>NS</s2></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Vertebrata</s0><s2>NS</s2></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Virose</s0></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Viral disease</s0></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Virosis</s0></fC07><fC07 i1="06" i2="X" l="FRE"><s0>Infection</s0></fC07><fC07 i1="06" i2="X" l="ENG"><s0>Infection</s0></fC07><fC07 i1="06" i2="X" l="SPA"><s0>Infección</s0></fC07><fN21><s1>215</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist></record>Pour manipuler ce document sous Unix (Dilib)
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|texte= A live attenuated H7N3 influenza virus vaccine is well tolerated and immunogenic in a Phase I trial in healthy adults
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