Preservation of the Immunogenicity of Dry-powder Influenza H5N1 Whole Inactivated Virus Vaccine at Elevated Storage Temperatures
Identifieur interne : 000908 ( Pmc/Checkpoint ); précédent : 000907; suivant : 000909Preservation of the Immunogenicity of Dry-powder Influenza H5N1 Whole Inactivated Virus Vaccine at Elevated Storage Temperatures
Auteurs : Felix Geeraedts [Pays-Bas] ; Vinay Saluja [Pays-Bas] ; Wouter Ter Veer [Pays-Bas] ; Jean-Pierre Amorij [Pays-Bas] ; Henderik W. Frijlink [Pays-Bas] ; Jan Wilschut [Pays-Bas] ; Wouter L. J. Hinrichs [Pays-Bas] ; Anke Huckriede [Pays-Bas]Source :
- The AAPS Journal [ 1550-7416 ] ; 2010.
Abstract
Stockpiling of pre-pandemic influenza vaccines guarantees immediate vaccine availability to counteract an emerging pandemic. Generally, influenza vaccines need to be stored and handled refrigerated to prevent thermal degradation of the antigenic component. Requirement of a cold-chain, however, complicates stockpiling and the logistics of vaccine distribution. We, therefore, investigated the effect of elevated storage temperatures on the immunogenicity of a pre-pandemic influenza A H5N1 whole inactivated virus vaccine. Either suspended in liquid or kept as a freeze-dried powder, vaccines could be stored for 1 year at ambient temperature (20°C) with minimal loss of immunogenicity in mice. Elevation of the storage temperature to 40°C, however, resulted in a significant loss of immunogenic potency within 3 months if vaccines were stored in liquid suspension. In sharp contrast, freeze-dried powder formulations were stable at 40°C for at least 3 months. The presence of inulin or trehalose sugar excipients during freeze-drying of the vaccine proved to be critical to maintain its immunogenic potency during storage, and to preserve the characteristic Th1-type response to whole inactivated virus vaccine. These results indicate that whole inactivated virus vaccines may be stored and handled at room temperature in moderate climate zones for over a year with minimal decline and, if converted to dry-powder, even in hot climate zones for at least 3 months. The increased stability of dry-powder vaccine at 40°C may also point to an extended shelf-life when stored at 4°C. Use of the more stable dry-powder formulation could simplify stockpiling and thereby facilitating successful pandemic intervention.
Url:
DOI: 10.1208/s12248-010-9179-z
PubMed: 20195930
PubMed Central: 2844510
Affiliations:
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<front><div type="abstract" xml:lang="en"><p>Stockpiling of pre-pandemic influenza vaccines guarantees immediate vaccine availability to counteract an emerging pandemic. Generally, influenza vaccines need to be stored and handled refrigerated to prevent thermal degradation of the antigenic component. Requirement of a cold-chain, however, complicates stockpiling and the logistics of vaccine distribution. We, therefore, investigated the effect of elevated storage temperatures on the immunogenicity of a pre-pandemic influenza A H5N1 whole inactivated virus vaccine. Either suspended in liquid or kept as a freeze-dried powder, vaccines could be stored for 1 year at ambient temperature (20°C) with minimal loss of immunogenicity in mice. Elevation of the storage temperature to 40°C, however, resulted in a significant loss of immunogenic potency within 3 months if vaccines were stored in liquid suspension. In sharp contrast, freeze-dried powder formulations were stable at 40°C for at least 3 months. The presence of inulin or trehalose sugar excipients during freeze-drying of the vaccine proved to be critical to maintain its immunogenic potency during storage, and to preserve the characteristic Th1-type response to whole inactivated virus vaccine. These results indicate that whole inactivated virus vaccines may be stored and handled at room temperature in moderate climate zones for over a year with minimal decline and, if converted to dry-powder, even in hot climate zones for at least 3 months. The increased stability of dry-powder vaccine at 40°C may also point to an extended shelf-life when stored at 4°C. Use of the more stable dry-powder formulation could simplify stockpiling and thereby facilitating successful pandemic intervention.</p>
</div>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">AAPS J</journal-id>
<journal-id journal-id-type="iso-abbrev">AAPS J</journal-id>
<journal-title-group><journal-title>The AAPS Journal</journal-title>
</journal-title-group>
<issn pub-type="epub">1550-7416</issn>
<publisher><publisher-name>Springer US</publisher-name>
<publisher-loc>Boston</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">20195930</article-id>
<article-id pub-id-type="pmc">2844510</article-id>
<article-id pub-id-type="publisher-id">9179</article-id>
<article-id pub-id-type="doi">10.1208/s12248-010-9179-z</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Preservation of the Immunogenicity of Dry-powder Influenza H5N1 Whole Inactivated Virus Vaccine at Elevated Storage Temperatures</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Geeraedts</surname>
<given-names>Felix</given-names>
</name>
<xref ref-type="aff" rid="Aff1"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Saluja</surname>
<given-names>Vinay</given-names>
</name>
<xref ref-type="aff" rid="Aff2"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>ter Veer</surname>
<given-names>Wouter</given-names>
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<xref ref-type="aff" rid="Aff1"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Amorij</surname>
<given-names>Jean-Pierre</given-names>
</name>
<xref ref-type="aff" rid="Aff2"></xref>
<xref ref-type="aff" rid="Aff3"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Frijlink</surname>
<given-names>Henderik W.</given-names>
</name>
<xref ref-type="aff" rid="Aff2"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wilschut</surname>
<given-names>Jan</given-names>
</name>
<xref ref-type="aff" rid="Aff1"></xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Hinrichs</surname>
<given-names>Wouter L. J.</given-names>
</name>
<address><phone>+31-50-3632398</phone>
<fax>+31-50-3632500</fax>
<email>w.l.j.hinrichs@rug.nl</email>
</address>
<xref ref-type="aff" rid="Aff2"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Huckriede</surname>
<given-names>Anke</given-names>
</name>
<xref ref-type="aff" rid="Aff1"></xref>
</contrib>
<aff id="Aff1"><label></label>
Department of Medical Microbiology, Molecular Virology Section, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands</aff>
<aff id="Aff2"><label></label>
Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands</aff>
<aff id="Aff3"><label></label>
Research and Development Unit, The Netherlands Vaccine Institute, Bilthoven, The Netherlands</aff>
</contrib-group>
<pub-date pub-type="epub"><day>2</day>
<month>3</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="collection"><month>6</month>
<year>2010</year>
</pub-date>
<volume>12</volume>
<issue>2</issue>
<fpage>215</fpage>
<lpage>222</lpage>
<history><date date-type="received"><day>30</day>
<month>11</month>
<year>2009</year>
</date>
<date date-type="accepted"><day>1</day>
<month>2</month>
<year>2010</year>
</date>
</history>
<permissions><copyright-statement>© The Author(s) 2010</copyright-statement>
</permissions>
<abstract id="Abs1"><p>Stockpiling of pre-pandemic influenza vaccines guarantees immediate vaccine availability to counteract an emerging pandemic. Generally, influenza vaccines need to be stored and handled refrigerated to prevent thermal degradation of the antigenic component. Requirement of a cold-chain, however, complicates stockpiling and the logistics of vaccine distribution. We, therefore, investigated the effect of elevated storage temperatures on the immunogenicity of a pre-pandemic influenza A H5N1 whole inactivated virus vaccine. Either suspended in liquid or kept as a freeze-dried powder, vaccines could be stored for 1 year at ambient temperature (20°C) with minimal loss of immunogenicity in mice. Elevation of the storage temperature to 40°C, however, resulted in a significant loss of immunogenic potency within 3 months if vaccines were stored in liquid suspension. In sharp contrast, freeze-dried powder formulations were stable at 40°C for at least 3 months. The presence of inulin or trehalose sugar excipients during freeze-drying of the vaccine proved to be critical to maintain its immunogenic potency during storage, and to preserve the characteristic Th1-type response to whole inactivated virus vaccine. These results indicate that whole inactivated virus vaccines may be stored and handled at room temperature in moderate climate zones for over a year with minimal decline and, if converted to dry-powder, even in hot climate zones for at least 3 months. The increased stability of dry-powder vaccine at 40°C may also point to an extended shelf-life when stored at 4°C. Use of the more stable dry-powder formulation could simplify stockpiling and thereby facilitating successful pandemic intervention.</p>
</abstract>
<kwd-group xml:lang="en"><title>Key words</title>
<kwd>freeze-drying</kwd>
<kwd>inulin</kwd>
<kwd>pandemic influenza</kwd>
<kwd>vaccine stockpiling</kwd>
<kwd>whole inactivated influenza vaccine (H5N1)</kwd>
</kwd-group>
<custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name>
<meta-value>© American Association of Pharmaceutical Scientists 2010</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>Pays-Bas</li>
</country>
<region><li>Groningue (province)</li>
</region>
<settlement><li>Groningue</li>
</settlement>
<orgName><li>Université de Groningue</li>
</orgName>
</list>
<tree><country name="Pays-Bas"><region name="Groningue (province)"><name sortKey="Geeraedts, Felix" sort="Geeraedts, Felix" uniqKey="Geeraedts F" first="Felix" last="Geeraedts">Felix Geeraedts</name>
</region>
<name sortKey="Amorij, Jean Pierre" sort="Amorij, Jean Pierre" uniqKey="Amorij J" first="Jean-Pierre" last="Amorij">Jean-Pierre Amorij</name>
<name sortKey="Amorij, Jean Pierre" sort="Amorij, Jean Pierre" uniqKey="Amorij J" first="Jean-Pierre" last="Amorij">Jean-Pierre Amorij</name>
<name sortKey="Frijlink, Henderik W" sort="Frijlink, Henderik W" uniqKey="Frijlink H" first="Henderik W." last="Frijlink">Henderik W. Frijlink</name>
<name sortKey="Hinrichs, Wouter L J" sort="Hinrichs, Wouter L J" uniqKey="Hinrichs W" first="Wouter L. J." last="Hinrichs">Wouter L. J. Hinrichs</name>
<name sortKey="Huckriede, Anke" sort="Huckriede, Anke" uniqKey="Huckriede A" first="Anke" last="Huckriede">Anke Huckriede</name>
<name sortKey="Saluja, Vinay" sort="Saluja, Vinay" uniqKey="Saluja V" first="Vinay" last="Saluja">Vinay Saluja</name>
<name sortKey="Ter Veer, Wouter" sort="Ter Veer, Wouter" uniqKey="Ter Veer W" first="Wouter" last="Ter Veer">Wouter Ter Veer</name>
<name sortKey="Wilschut, Jan" sort="Wilschut, Jan" uniqKey="Wilschut J" first="Jan" last="Wilschut">Jan Wilschut</name>
</country>
</tree>
</affiliations>
</record>
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