Pandemic Influenza Vaccines – The Challenges
Identifieur interne : 000E44 ( Pmc/Curation ); précédent : 000E43; suivant : 000E45Pandemic Influenza Vaccines – The Challenges
Auteurs : Lars R. Haaheim [Norvège] ; Abdullah S. Madhun ; Rebecca CoxSource :
- Viruses [ 1999-4915 ] ; 2009.
Abstract
Recent years’ enzootic spread of highly pathogenic H5N1 virus among poultry and the many lethal zoonoses in its wake has stimulated basic and applied pandemic vaccine research. The quest for an efficacious, affordable and timely accessible pandemic vaccine has been high on the agenda. When a variant H1N1 strain of swine origin emerged as a pandemic virus, it surprised many, as this subtype is well-known to man as a seasonal virus. This review will cover some difficult vaccine questions, such as the immunological challenges, the new production platforms, and the limited supply and global equity issues.
Url:
DOI: 10.3390/v1031089
PubMed: 21994584
PubMed Central: 3185517
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Pandemic Influenza Vaccines – The Challenges</title><author><name sortKey="Haaheim, Lars R" sort="Haaheim, Lars R" uniqKey="Haaheim L" first="Lars R." last="Haaheim">Lars R. Haaheim</name><affiliation wicri:level="1"><nlm:aff id="af1-viruses-01-01089"> Myrdalskogen 95, N-5117 Ulset, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea> Myrdalskogen 95, N-5117 Ulset</wicri:regionArea></affiliation></author><author><name sortKey="Madhun, Abdullah S" sort="Madhun, Abdullah S" uniqKey="Madhun A" first="Abdullah S." last="Madhun">Abdullah S. Madhun</name><affiliation><nlm:aff id="af2-viruses-01-01089"> Influenza Centre, The Gade Institute, University of Bergen, Laboratory Building, 5th Floor, Haukeland University Hospital, N-5021 Bergen, Norway; E-Mails:<email>abdullah.madhun@gades.uib.no</email> (A.S.M.);<email>Rebecca.Cox@gades.uib.no</email> (R.C.)</nlm:aff></affiliation></author><author><name sortKey="Cox, Rebecca" sort="Cox, Rebecca" uniqKey="Cox R" first="Rebecca" last="Cox">Rebecca Cox</name><affiliation><nlm:aff id="af2-viruses-01-01089"> Influenza Centre, The Gade Institute, University of Bergen, Laboratory Building, 5th Floor, Haukeland University Hospital, N-5021 Bergen, Norway; E-Mails:<email>abdullah.madhun@gades.uib.no</email> (A.S.M.);<email>Rebecca.Cox@gades.uib.no</email> (R.C.)</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21994584</idno><idno type="pmc">3185517</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185517</idno><idno type="RBID">PMC:3185517</idno><idno type="doi">10.3390/v1031089</idno><date when="2009">2009</date><idno type="wicri:Area/Pmc/Corpus">000E44</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000E44</idno><idno type="wicri:Area/Pmc/Curation">000E44</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000E44</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Pandemic Influenza Vaccines – The Challenges</title><author><name sortKey="Haaheim, Lars R" sort="Haaheim, Lars R" uniqKey="Haaheim L" first="Lars R." last="Haaheim">Lars R. Haaheim</name><affiliation wicri:level="1"><nlm:aff id="af1-viruses-01-01089"> Myrdalskogen 95, N-5117 Ulset, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea> Myrdalskogen 95, N-5117 Ulset</wicri:regionArea></affiliation></author><author><name sortKey="Madhun, Abdullah S" sort="Madhun, Abdullah S" uniqKey="Madhun A" first="Abdullah S." last="Madhun">Abdullah S. Madhun</name><affiliation><nlm:aff id="af2-viruses-01-01089"> Influenza Centre, The Gade Institute, University of Bergen, Laboratory Building, 5th Floor, Haukeland University Hospital, N-5021 Bergen, Norway; E-Mails:<email>abdullah.madhun@gades.uib.no</email> (A.S.M.);<email>Rebecca.Cox@gades.uib.no</email> (R.C.)</nlm:aff></affiliation></author><author><name sortKey="Cox, Rebecca" sort="Cox, Rebecca" uniqKey="Cox R" first="Rebecca" last="Cox">Rebecca Cox</name><affiliation><nlm:aff id="af2-viruses-01-01089"> Influenza Centre, The Gade Institute, University of Bergen, Laboratory Building, 5th Floor, Haukeland University Hospital, N-5021 Bergen, Norway; E-Mails:<email>abdullah.madhun@gades.uib.no</email> (A.S.M.);<email>Rebecca.Cox@gades.uib.no</email> (R.C.)</nlm:aff></affiliation></author></analytic><series><title level="j">Viruses</title><idno type="eISSN">1999-4915</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Recent years’ enzootic spread of highly pathogenic H5N1 virus among poultry and the many lethal zoonoses in its wake has stimulated basic and applied pandemic vaccine research. The quest for an efficacious, affordable and timely accessible pandemic vaccine has been high on the agenda. When a variant H1N1 strain of swine origin emerged as a pandemic virus, it surprised many, as this subtype is well-known to man as a seasonal virus. This review will cover some difficult vaccine questions, such as the immunological challenges, the new production platforms, and the limited supply and global equity issues.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Zimmer, Sm" uniqKey="Zimmer S">SM Zimmer</name></author><author><name sortKey="Burke, Ds" uniqKey="Burke D">DS Burke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fraser, C" uniqKey="Fraser C">C Fraser</name></author><author><name sortKey="Donnelly, Ca" uniqKey="Donnelly C">CA Donnelly</name></author><author><name sortKey="Cauchemez, S" uniqKey="Cauchemez S">S Cauchemez</name></author><author><name sortKey="Hanage, Wp" uniqKey="Hanage W">WP Hanage</name></author><author><name sortKey="Van Kerkhove, Md" uniqKey="Van Kerkhove M">MD Van Kerkhove</name></author><author><name sortKey="Hollingsworth, Td" uniqKey="Hollingsworth T">TD 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Viruses</journal-id><journal-title-group><journal-title>Viruses</journal-title></journal-title-group><issn pub-type="epub">1999-4915</issn><publisher><publisher-name>Molecular Diversity Preservation International (MDPI)</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">21994584</article-id><article-id pub-id-type="pmc">3185517</article-id><article-id pub-id-type="doi">10.3390/v1031089</article-id><article-id pub-id-type="publisher-id">viruses-01-01089</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Pandemic Influenza Vaccines – The Challenges</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Haaheim</surname><given-names>Lars R.</given-names></name><xref ref-type="aff" rid="af1-viruses-01-01089"><sup>1</sup></xref><xref ref-type="corresp" rid="c1-viruses-01-01089"><sup>*</sup></xref></contrib><contrib contrib-type="author"><name><surname>Madhun</surname><given-names>Abdullah S.</given-names></name><xref ref-type="aff" rid="af2-viruses-01-01089"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cox</surname><given-names>Rebecca</given-names></name><xref ref-type="aff" rid="af2-viruses-01-01089"><sup>2</sup></xref></contrib></contrib-group><aff id="af1-viruses-01-01089"><label>1</label> Myrdalskogen 95, N-5117 Ulset, Norway</aff><aff id="af2-viruses-01-01089"><label>2</label> Influenza Centre, The Gade Institute, University of Bergen, Laboratory Building, 5th Floor, Haukeland University Hospital, N-5021 Bergen, Norway; E-Mails:<email>abdullah.madhun@gades.uib.no</email> (A.S.M.);<email>Rebecca.Cox@gades.uib.no</email> (R.C.)</aff><author-notes><corresp id="c1-viruses-01-01089"><label>*</label>Author to whom correspondence should be addressed; E-Mail: <email>lars.haaheim@gades.uib.no</email>; Tel.: +47-924 17 076; Fax: +47-55 97 46 89.</corresp></author-notes><pub-date pub-type="collection"><month>12</month><year>2009</year></pub-date><pub-date pub-type="epub"><day>3</day><month>12</month><year>2009</year></pub-date><volume>1</volume><issue>3</issue><fpage>1089</fpage><lpage>1109</lpage><history><date date-type="received"><day>14</day><month>8</month><year>2009</year></date><date date-type="rev-recd"><day>26</day><month>11</month><year>2009</year></date><date date-type="accepted"><day>1</day><month>12</month><year>2009</year></date></history><permissions><copyright-statement>© 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.</copyright-statement><copyright-year>2009</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/3.0"><license-p><pmc-comment>CREATIVE COMMONS</pmc-comment>This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/3.0/">http://creativecommons.org/licenses/by/3.0/</ext-link>).</license-p></license></permissions><abstract><p>Recent years’ enzootic spread of highly pathogenic H5N1 virus among poultry and the many lethal zoonoses in its wake has stimulated basic and applied pandemic vaccine research. The quest for an efficacious, affordable and timely accessible pandemic vaccine has been high on the agenda. When a variant H1N1 strain of swine origin emerged as a pandemic virus, it surprised many, as this subtype is well-known to man as a seasonal virus. This review will cover some difficult vaccine questions, such as the immunological challenges, the new production platforms, and the limited supply and global equity issues.</p></abstract><kwd-group><kwd>influenza</kwd><kwd>H5N1</kwd><kwd>H1N1</kwd><kwd>pandemic</kwd><kwd>vaccine</kwd><kwd>haemagglutinin (HA)</kwd><kwd>neuraminidase (NA)</kwd></kwd-group></article-meta></front><floats-group><table-wrap id="t1-viruses-01-01089" position="float"><label>Table 1.</label><caption><p>Main properties of the most widely used influenza vaccines.</p></caption><table frame="box" rules="all"><thead><tr><th align="center" valign="middle" rowspan="1" colspan="1">Type of influenza vaccine</th><th align="center" valign="middle" rowspan="1" colspan="1">Substrate <xref ref-type="table-fn" rid="tfn1-viruses-01-01089"><sup>1)</sup></xref></th><th align="center" valign="middle" rowspan="1" colspan="1">Route of administration</th><th align="center" valign="middle" rowspan="1" colspan="1">Immune response <xref ref-type="table-fn" rid="tfn2-viruses-01-01089"><sup>2)</sup></xref></th><th align="center" valign="middle" rowspan="1" colspan="1">Immunological challenges</th><th align="center" valign="middle" rowspan="1" colspan="1">Comments</th></tr></thead><tbody><tr><td align="center" valign="middle" content-type="background-color:#CCFFCC" rowspan="1" colspan="1"><bold>Inactivated</bold></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" content-type="background-color:#CCFFCC" rowspan="1" colspan="1">No apparent stimulation of mucosal immunity</td><td align="left" valign="middle" rowspan="1" colspan="1"></td></tr><tr><td align="right" valign="middle" content-type="background-color:#CCFFCC" rowspan="1" colspan="1">Whole virion</td><td align="center" valign="middle" rowspan="3" colspan="1">Embryonated eggs, cell culture</td><td align="center" valign="middle" rowspan="3" content-type="background-color:#CCFFCC" colspan="1">intramuscular</td><td align="center" valign="middle" rowspan="1" colspan="1">Strong, mixed Th1/Th2</td><td align="center" valign="middle" content-type="background-color:#CCFFCC" rowspan="1" colspan="1"></td><td align="left" valign="middle" rowspan="3" colspan="1">Supply of embryonated eggs is a limiting factor.<break></break>Cell-grown vaccine production more scalable.</td></tr><tr><td align="right" valign="middle" content-type="background-color:#CCFFCC" rowspan="1" colspan="1">Split</td><td align="center" valign="middle" rowspan="1" colspan="1">Mostly Th2</td><td align="center" valign="middle" content-type="background-color:#CCFFCC" rowspan="1" colspan="1">Should be adjuvanted</td></tr><tr><td align="right" valign="middle" content-type="background-color:#CCFFCC" rowspan="1" colspan="1">Subunit (HA and NA)</td><td align="center" valign="middle" rowspan="1" colspan="1">Mostly Th2</td><td align="center" valign="middle" content-type="background-color:#CCFFCC" rowspan="1" colspan="1">Least immunogenic, should be adjuvanted</td></tr><tr><td align="center" valign="middle" content-type="background-color:#CCFFCC" rowspan="1" colspan="1"><bold>Live attenuated</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">Embryonated eggs</td><td align="center" valign="middle" content-type="background-color:#CCFFCC" rowspan="1" colspan="1">intranasal</td><td align="center" valign="middle" rowspan="1" colspan="1">Humoral, cellular, mucosal</td><td align="center" valign="middle" content-type="background-color:#CCFFCC" rowspan="1" colspan="1">Should perform better in the elderly</td><td align="left" valign="middle" rowspan="1" colspan="1">Rapid and large vaccine output. Easily scalable production.<break></break>Cannot be used in the very young and the immunocompromised.</td></tr></tbody></table><table-wrap-foot><fn id="tfn1-viruses-01-01089"><label>1)</label><p>MDCK (Madin Darby Canine Kidney cells), Vero (African green monkey kidney cells), PerC6<sup>®</sup> (human embryonic retinal cells);</p></fn><fn id="tfn2-viruses-01-01089"><label>2)</label><p>Th1 and Th2 are T-cell subsets heralding cellular and humoral response, respectively.</p></fn></table-wrap-foot></table-wrap><table-wrap id="t2-viruses-01-01089" position="float"><label>Table 2.</label><caption><p>Reassortant vaccine strains used in clinical trials of pandemic vaccines [<xref ref-type="bibr" rid="b18-viruses-01-01089">18</xref>].</p></caption><table frame="box" rules="all"><thead><tr><th align="left" valign="bottom" rowspan="1" colspan="1">Virus strain</th><th align="left" valign="bottom" rowspan="1" colspan="1">Subtype</th></tr></thead><tbody><tr content-type="background-color:#CCFFCC"><td align="left" valign="top" rowspan="1" colspan="1">A/Singapore/1/57</td><td align="left" valign="top" rowspan="1" colspan="1">H2N2</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">A/duck/Singapore/97</td><td align="left" valign="top" rowspan="1" colspan="1">H5N1</td></tr><tr content-type="background-color:#CCFFCC"><td align="left" valign="top" rowspan="1" colspan="1">A/Viet Nam/1194/2004 (NIBRG-14), clade 1</td><td align="left" valign="top" rowspan="1" colspan="1">H5N1</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">A/Indonesia/5/2005, clade 2.1</td><td align="left" valign="top" rowspan="1" colspan="1">H5N1</td></tr><tr content-type="background-color:#CCFFCC"><td align="left" valign="top" rowspan="1" colspan="1">A/duck/Potsdam/88/92 (H5N2) × A/Leningrad/134/17/57 (H2N2)</td><td align="left" valign="top" rowspan="1" colspan="1">H5N2 (live)</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">A/chicken/Italy H7N1×PR8 (RD-3)</td><td align="left" valign="top" rowspan="1" colspan="1">H7N1</td></tr><tr content-type="background-color:#CCFFCC"><td align="left" valign="top" rowspan="1" colspan="1">A/chicken/British Columbia/CN-6/2004</td><td align="left" valign="top" rowspan="1" colspan="1">H7N3</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">A/Hong Kong/1073/99</td><td align="left" valign="top" rowspan="1" colspan="1">H9N2</td></tr><tr content-type="background-color:#CCFFCC"><td align="left" valign="top" rowspan="1" colspan="1">A/chicken/HongKong/G9/97 (H9N2) × A/AnnArbor/6/60 (H2N2)</td><td align="left" valign="top" rowspan="1" colspan="1">H9N2 (live)</td></tr></tbody></table></table-wrap><table-wrap id="t3-viruses-01-01089" position="float"><label>Table 3.</label><caption><p>Different scenarios for global availability of (monovalent) pandemic vaccine 2010. Vaccine courses in millions.</p></caption><table frame="box" rules="all"><thead><tr><th align="center" valign="bottom" rowspan="1" colspan="1"></th><th colspan="2" align="center" valign="bottom" rowspan="1">1 dose to all</th><th colspan="2" align="center" valign="bottom" rowspan="1">2 doses to all</th><th colspan="2" align="center" valign="bottom" rowspan="1">70% 1 dose, 30% 2 doses</th></tr><tr><th align="center" valign="middle" content-type="background-color:#CCFFCC" rowspan="1" colspan="1">HA per dose</th><th align="center" valign="middle" rowspan="1" colspan="1">No of vaccination courses</th><th align="center" valign="middle" content-type="background-color:#CCFFCC" rowspan="1" colspan="1">Global coverage</th><th align="center" valign="middle" rowspan="1" colspan="1">No of vaccination courses</th><th align="center" valign="middle" content-type="background-color:#CCFFCC" rowspan="1" colspan="1">Global coverage</th><th align="center" valign="middle" rowspan="1" colspan="1">No of vaccination courses</th><th align="center" valign="middle" content-type="background-color:#CCFFCC" rowspan="1" colspan="1">Global coverage</th></tr></thead><tbody><tr><td align="center" valign="bottom" content-type="background-color:#CCFFCC" rowspan="1" colspan="1">15 μg</td><td align="center" valign="bottom" rowspan="1" colspan="1">3,000</td><td align="center" valign="bottom" content-type="background-color:#CCFFCC" rowspan="1" colspan="1">45%</td><td align="center" valign="bottom" rowspan="1" colspan="1">1,500</td><td align="center" valign="bottom" content-type="background-color:#CCFFCC" rowspan="1" colspan="1">22%</td><td align="center" valign="bottom" rowspan="1" colspan="1">2,300</td><td align="center" valign="bottom" content-type="background-color:#CCFFCC" rowspan="1" colspan="1">34%</td></tr><tr><td align="center" valign="bottom" content-type="background-color:#CCFFCC" rowspan="1" colspan="1">10 μg</td><td align="center" valign="bottom" rowspan="1" colspan="1">4,500</td><td align="center" valign="bottom" content-type="background-color:#CCFFCC" rowspan="1" colspan="1">67%</td><td align="center" valign="bottom" rowspan="1" colspan="1">2,250</td><td align="center" valign="bottom" content-type="background-color:#CCFFCC" rowspan="1" colspan="1">34%</td><td align="center" valign="bottom" rowspan="1" colspan="1">3,450</td><td align="center" valign="bottom" content-type="background-color:#CCFFCC" rowspan="1" colspan="1">52%</td></tr><tr><td align="center" valign="bottom" content-type="background-color:#CCFFCC" rowspan="1" colspan="1">5 μg</td><td align="center" valign="bottom" rowspan="1" colspan="1">9,000</td><td align="center" valign="bottom" content-type="background-color:#CCFFCC" rowspan="1" colspan="1">>100%</td><td align="center" valign="bottom" rowspan="1" colspan="1">4,500</td><td align="center" valign="bottom" content-type="background-color:#CCFFCC" rowspan="1" colspan="1">67%</td><td align="center" valign="bottom" rowspan="1" colspan="1">6,900</td><td align="center" valign="bottom" content-type="background-color:#CCFFCC" rowspan="1" colspan="1">>100 %</td></tr></tbody></table><table-wrap-foot><fn id="tfn3-viruses-01-01089"><p>Calculations are based on an estimated global production capacity of trivalent seasonal influenza vaccines to be 1 billion doses in 2010, each with 15 μg HA, and a global population of 6.7 billion.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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