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Phase I/II Randomized Double-Blind Study of the Safety and Immunogenicity of a Nonadjuvanted Vero Cell Culture-Derived Whole-Virus H9N2 Influenza Vaccine in Healthy Adults

Identifieur interne : 000617 ( Pmc/Corpus ); précédent : 000616; suivant : 000618

Phase I/II Randomized Double-Blind Study of the Safety and Immunogenicity of a Nonadjuvanted Vero Cell Culture-Derived Whole-Virus H9N2 Influenza Vaccine in Healthy Adults

Auteurs : Gerald Aichinger ; Barbara Grohmann-Izay ; Maikel V. W. Van Der Velden ; Sandor Fritsch ; Manuela Koska ; Daniel Portsmouth ; Mary Kate Hart ; Wael El-Amin ; Otfried Kistner ; P. Noel Barrett

Source :

RBID : PMC:4278922

Abstract

Studies on candidate pandemic vaccines against avian influenza viruses have focused on H5N1, but viruses of other subtypes, such as A/H9N2, are also considered to have pandemic potential. We investigated the safety and immunogenicity of two immunizations with one of five different antigen doses (ranging from 3.75 to 45 μg of hemagglutinin antigen) of a nonadjuvanted whole-virus G9 lineage H9N2 influenza virus vaccine in healthy adults aged 18 to 49 years. The antibody responses were measured by hemagglutination inhibition (HI), microneutralization (MN), and single radial hemolysis (SRH) assays. To investigate a hypothesis that previous exposure to H2N2 viruses in subjects born in or before 1968 might prime for more robust antibody responses to H9N2 vaccination than that in subjects born after 1968, a post hoc age-stratified analysis of antibody responses was done. Both vaccinations in all dose groups were safe and well tolerated. No vaccine-related serious adverse events were reported, and the majority of the adverse reactions were rated as mild. The rates of injection site reactions were lower in the 3.75-μg- and 7.5-μg-dose groups than those in the higher-dose groups; the rates of systemic reactions were similar across all dose groups. The seroprotection rates among the different dose groups 21 days after the second immunization ranged from 52.8% to 88.9% as measured by HI assay, from 88.7% to 98.1% or 82.7% to 96.2% as measured by MN assay (MN titer cutoffs, 1:40 and 1:80, respectively), and from 94.2% to 100% as measured by SRH assay. Higher antibody responses were not induced in subjects born in or before 1968. These data indicate that a nonadjuvanted whole-virus H9N2 vaccine is well tolerated and immunogenic in healthy adults. (This study has been registered at ClinicalTrials.gov under registration no. NCT01320696.)


Url:
DOI: 10.1128/CVI.00275-14
PubMed: 25355797
PubMed Central: 4278922

Links to Exploration step

PMC:4278922

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<name sortKey="Barrett, P Noel" sort="Barrett, P Noel" uniqKey="Barrett P" first="P. Noel" last="Barrett">P. Noel Barrett</name>
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<p>Studies on candidate pandemic vaccines against avian influenza viruses have focused on H5N1, but viruses of other subtypes, such as A/H9N2, are also considered to have pandemic potential. We investigated the safety and immunogenicity of two immunizations with one of five different antigen doses (ranging from 3.75 to 45 μg of hemagglutinin antigen) of a nonadjuvanted whole-virus G9 lineage H9N2 influenza virus vaccine in healthy adults aged 18 to 49 years. The antibody responses were measured by hemagglutination inhibition (HI), microneutralization (MN), and single radial hemolysis (SRH) assays. To investigate a hypothesis that previous exposure to H2N2 viruses in subjects born in or before 1968 might prime for more robust antibody responses to H9N2 vaccination than that in subjects born after 1968, a
<italic>post hoc</italic>
age-stratified analysis of antibody responses was done. Both vaccinations in all dose groups were safe and well tolerated. No vaccine-related serious adverse events were reported, and the majority of the adverse reactions were rated as mild. The rates of injection site reactions were lower in the 3.75-μg- and 7.5-μg-dose groups than those in the higher-dose groups; the rates of systemic reactions were similar across all dose groups. The seroprotection rates among the different dose groups 21 days after the second immunization ranged from 52.8% to 88.9% as measured by HI assay, from 88.7% to 98.1% or 82.7% to 96.2% as measured by MN assay (MN titer cutoffs, 1:40 and 1:80, respectively), and from 94.2% to 100% as measured by SRH assay. Higher antibody responses were not induced in subjects born in or before 1968. These data indicate that a nonadjuvanted whole-virus H9N2 vaccine is well tolerated and immunogenic in healthy adults. (This study has been registered at
<ext-link ext-link-type="uri" xlink:href="http://ClinicalTrials.gov">ClinicalTrials.gov</ext-link>
under registration no. NCT01320696.)</p>
</div>
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<journal-id journal-id-type="nlm-ta">Clin Vaccine Immunol</journal-id>
<journal-id journal-id-type="iso-abbrev">Clin. Vaccine Immunol</journal-id>
<journal-id journal-id-type="hwp">cdli</journal-id>
<journal-id journal-id-type="pmc">cvi</journal-id>
<journal-id journal-id-type="publisher-id">CVI</journal-id>
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<journal-title>Clinical and Vaccine Immunology : CVI</journal-title>
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<issn pub-type="ppub">1556-6811</issn>
<issn pub-type="epub">1556-679X</issn>
<publisher>
<publisher-name>American Society for Microbiology</publisher-name>
<publisher-loc>1752 N St., N.W., Washington, DC</publisher-loc>
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<article-id pub-id-type="pmid">25355797</article-id>
<article-id pub-id-type="pmc">4278922</article-id>
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<article-id pub-id-type="doi">10.1128/CVI.00275-14</article-id>
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<subject>Vaccines</subject>
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<title-group>
<article-title>Phase I/II Randomized Double-Blind Study of the Safety and Immunogenicity of a Nonadjuvanted Vero Cell Culture-Derived Whole-Virus H9N2 Influenza Vaccine in Healthy Adults</article-title>
<alt-title alt-title-type="running-head">Vero-Derived Whole-Virus H9N2 Vaccine in Adults</alt-title>
<alt-title alt-title-type="short-authors">Aichinger et al.</alt-title>
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<contrib contrib-type="author" corresp="yes">
<name>
<surname>Aichinger</surname>
<given-names>Gerald</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Grohmann-Izay</surname>
<given-names>Barbara</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>van der Velden</surname>
<given-names>Maikel V. W.</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Fritsch</surname>
<given-names>Sandor</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Koska</surname>
<given-names>Manuela</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Portsmouth</surname>
<given-names>Daniel</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>c</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hart</surname>
<given-names>Mary Kate</given-names>
</name>
<xref ref-type="aff" rid="aff4">
<sup>d</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>El-Amin</surname>
<given-names>Wael</given-names>
</name>
<xref ref-type="aff" rid="aff4">
<sup>d</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kistner</surname>
<given-names>Otfried</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>c</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Barrett</surname>
<given-names>P. Noel</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>c</sup>
</xref>
</contrib>
<aff id="aff1">
<label>a</label>
Vaccine R&D, Baxter BioScience, Vienna, Austria</aff>
<aff id="aff2">
<label>b</label>
Global R&D, Baxter BioScience, Vienna, Austria</aff>
<aff id="aff3">
<label>c</label>
Vaccine R&D, Baxter BioScience, Orth/Donau, Austria</aff>
<aff id="aff4">
<label>d</label>
DynPort Vaccine Company, Frederick, Maryland, USA</aff>
</contrib-group>
<contrib-group>
<contrib contrib-type="editor">
<name>
<surname>Plotkin</surname>
<given-names>S. A.</given-names>
</name>
<role>Editor</role>
</contrib>
</contrib-group>
<author-notes>
<corresp id="cor1">Address correspondence to Gerald Aichinger,
<email>gerald_aichinger@baxter.com</email>
.</corresp>
<fn fn-type="other">
<p>
<bold>Citation</bold>
Aichinger G, Grohmann-Izay B, van der Velden MVW, Fritsch S, Koska M, Portsmouth D, Hart MK, El-Amin W, Kistner O, Barrett PN. 2015. Phase I/II randomized double-blind study of the safety and immunogenicity of a nonadjuvanted Vero cell culture-derived whole-virus H9N2 influenza vaccine in healthy adults. Clin Vaccine Immunol 22:46–55. doi:
<ext-link ext-link-type="uri" xlink:href="http://dx.doi.org/10.1128/CVI.00275-14">10.1128/CVI.00275-14</ext-link>
.</p>
</fn>
</author-notes>
<pub-date pub-type="epreprint">
<day>29</day>
<month>10</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="epub">
<day>30</day>
<month>12</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="ppub">
<month>1</month>
<year>2015</year>
</pub-date>
<volume>22</volume>
<issue>1</issue>
<fpage>46</fpage>
<lpage>55</lpage>
<history>
<date date-type="received">
<day>12</day>
<month>5</month>
<year>2014</year>
</date>
<date date-type="rev-request">
<day>18</day>
<month>6</month>
<year>2014</year>
</date>
<date date-type="accepted">
<day>23</day>
<month>10</month>
<year>2014</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2015, American Society for Microbiology. All Rights Reserved.</copyright-statement>
<copyright-year>2015</copyright-year>
<copyright-holder>American Society for Microbiology</copyright-holder>
</permissions>
<self-uri content-type="pdf" xlink:href="zcd00115000046.pdf"></self-uri>
<abstract>
<p>Studies on candidate pandemic vaccines against avian influenza viruses have focused on H5N1, but viruses of other subtypes, such as A/H9N2, are also considered to have pandemic potential. We investigated the safety and immunogenicity of two immunizations with one of five different antigen doses (ranging from 3.75 to 45 μg of hemagglutinin antigen) of a nonadjuvanted whole-virus G9 lineage H9N2 influenza virus vaccine in healthy adults aged 18 to 49 years. The antibody responses were measured by hemagglutination inhibition (HI), microneutralization (MN), and single radial hemolysis (SRH) assays. To investigate a hypothesis that previous exposure to H2N2 viruses in subjects born in or before 1968 might prime for more robust antibody responses to H9N2 vaccination than that in subjects born after 1968, a
<italic>post hoc</italic>
age-stratified analysis of antibody responses was done. Both vaccinations in all dose groups were safe and well tolerated. No vaccine-related serious adverse events were reported, and the majority of the adverse reactions were rated as mild. The rates of injection site reactions were lower in the 3.75-μg- and 7.5-μg-dose groups than those in the higher-dose groups; the rates of systemic reactions were similar across all dose groups. The seroprotection rates among the different dose groups 21 days after the second immunization ranged from 52.8% to 88.9% as measured by HI assay, from 88.7% to 98.1% or 82.7% to 96.2% as measured by MN assay (MN titer cutoffs, 1:40 and 1:80, respectively), and from 94.2% to 100% as measured by SRH assay. Higher antibody responses were not induced in subjects born in or before 1968. These data indicate that a nonadjuvanted whole-virus H9N2 vaccine is well tolerated and immunogenic in healthy adults. (This study has been registered at
<ext-link ext-link-type="uri" xlink:href="http://ClinicalTrials.gov">ClinicalTrials.gov</ext-link>
under registration no. NCT01320696.)</p>
</abstract>
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