Development of a Freeze-Dried, Heat-Stable Influenza Subunit Vaccine Formulation
Identifieur interne : 000C48 ( Pmc/Curation ); précédent : 000C47; suivant : 000C49Development of a Freeze-Dried, Heat-Stable Influenza Subunit Vaccine Formulation
Auteurs : Alexander Flood [États-Unis] ; Marcus Estrada [États-Unis] ; David Mcadams [États-Unis] ; Yuhua Ji [États-Unis] ; Dexiang Chen [États-Unis]Source :
- PLoS ONE [ 1932-6203 ] ; 2016.
Abstract
An influenza pandemic remains a major public health concern. A key strategy to prevent a pandemic is to stockpile and pre-position stable influenza vaccine to allow rapid deployment in response to an outbreak. However, most influenza vaccines today are formulated as liquids that are stable only within a temperature range of 2°C to 8°C and require use of a cold chain, making vaccine transportation, distribution, and storage complicated and expensive, particularly for developing countries. To support the National Strategy for Pandemic Influenza preparedness in the United States and internationally, we developed two lead dry formulations of stable H1N1 influenza subunit vaccines using freeze-drying technology. The stable formulations contain an excipient combination of a disaccharide, such as sucrose or trehalose, and glycine, in addition to a surfactant and phosphate buffer. The freeze-dried vaccines were shown to be safe and remained immunogenic in an in vivo study in mice. Moreover, the lead formulations demonstrated no significant loss of activity after 40 months at storage temperatures of 25°C and 37°C. This stability can be particularly attractive as it could eliminate the need to use a cold chain for vaccine deployment and facilitate integration of vaccine distribution with general drug distribution where appropriate. These freeze-dried thermostable influenza subunit vaccines could also reduce the frequency of vaccine stockpile turnover, offering a cost-effective option for pandemic preparedness.
Url:
DOI: 10.1371/journal.pone.0164692
PubMed: 27851765
PubMed Central: 5112892
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D" first="Dexiang" last="Chen">Dexiang Chen</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Devices and Tools Program, PATH, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Devices and Tools Program, PATH, Seattle, Washington</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27851765</idno><idno type="pmc">5112892</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112892</idno><idno type="RBID">PMC:5112892</idno><idno type="doi">10.1371/journal.pone.0164692</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000C48</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000C48</idno><idno type="wicri:Area/Pmc/Curation">000C48</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000C48</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Development of a Freeze-Dried, Heat-Stable Influenza Subunit Vaccine Formulation</title><author><name sortKey="Flood, Alexander" sort="Flood, Alexander" uniqKey="Flood A" first="Alexander" last="Flood">Alexander Flood</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Devices and Tools Program, PATH, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Devices and Tools Program, PATH, Seattle, Washington</wicri:regionArea></affiliation></author><author><name sortKey="Estrada, Marcus" sort="Estrada, Marcus" uniqKey="Estrada M" first="Marcus" last="Estrada">Marcus Estrada</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Devices and Tools Program, PATH, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Devices and Tools Program, PATH, Seattle, Washington</wicri:regionArea></affiliation></author><author><name sortKey="Mcadams, David" sort="Mcadams, David" uniqKey="Mcadams D" first="David" last="Mcadams">David Mcadams</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Devices and Tools Program, PATH, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Devices and Tools Program, PATH, Seattle, Washington</wicri:regionArea></affiliation></author><author><name sortKey="Ji, Yuhua" sort="Ji, Yuhua" uniqKey="Ji Y" first="Yuhua" last="Ji">Yuhua Ji</name><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Drug Development Program, PATH, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Drug Development Program, PATH, Seattle, Washington</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Dexiang" sort="Chen, Dexiang" uniqKey="Chen D" first="Dexiang" last="Chen">Dexiang Chen</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Devices and Tools Program, PATH, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Devices and Tools Program, PATH, Seattle, Washington</wicri:regionArea></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>An influenza pandemic remains a major public health concern. A key strategy to prevent a pandemic is to stockpile and pre-position stable influenza vaccine to allow rapid deployment in response to an outbreak. However, most influenza vaccines today are formulated as liquids that are stable only within a temperature range of 2°C to 8°C and require use of a cold chain, making vaccine transportation, distribution, and storage complicated and expensive, particularly for developing countries. To support the National Strategy for Pandemic Influenza preparedness in the United States and internationally, we developed two lead dry formulations of stable H1N1 influenza subunit vaccines using freeze-drying technology. The stable formulations contain an excipient combination of a disaccharide, such as sucrose or trehalose, and glycine, in addition to a surfactant and phosphate buffer. The freeze-dried vaccines were shown to be safe and remained immunogenic in an in vivo study in mice. Moreover, the lead formulations demonstrated no significant loss of activity after 40 months at storage temperatures of 25°C and 37°C. This stability can be particularly attractive as it could eliminate the need to use a cold chain for vaccine deployment and facilitate integration of vaccine distribution with general drug distribution where appropriate. These freeze-dried thermostable influenza subunit vaccines could also reduce the frequency of vaccine stockpile turnover, offering a cost-effective option for pandemic preparedness.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Orszag, Pr" uniqKey="Orszag P">PR Orszag</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Carter, Nj" uniqKey="Carter N">NJ Carter</name></author><author><name sortKey="Curran, Mp" uniqKey="Curran M">MP Curran</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Coenen, F" uniqKey="Coenen F">F Coenen</name></author><author><name sortKey="Tolboom, Jt" uniqKey="Tolboom J">JT Tolboom</name></author><author><name sortKey="Frijlink, Hw" uniqKey="Frijlink H">HW Frijlink</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Luykx, Dm" uniqKey="Luykx D">DM Luykx</name></author><author><name sortKey="Casteleijn, Mg" uniqKey="Casteleijn M">MG Casteleijn</name></author><author><name sortKey="Jiskoot, W" uniqKey="Jiskoot W">W Jiskoot</name></author><author><name sortKey="Westdijk, J" uniqKey="Westdijk J">J Westdijk</name></author><author><name sortKey="Jongen, Pm" uniqKey="Jongen P">PM Jongen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, J" uniqKey="Huang J">J Huang</name></author><author><name sortKey="Garmise, Rj" uniqKey="Garmise R">RJ Garmise</name></author><author><name sortKey="Crowder, Tm" uniqKey="Crowder T">TM Crowder</name></author><author><name sortKey="Mar, K" uniqKey="Mar K">K Mar</name></author><author><name sortKey="Hwang, Cr" uniqKey="Hwang C">CR Hwang</name></author><author><name sortKey="Hickey, Aj" uniqKey="Hickey A">AJ Hickey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Amorij, Jp" uniqKey="Amorij J">JP Amorij</name></author><author><name sortKey="Huckriede, A" uniqKey="Huckriede A">A Huckriede</name></author><author><name sortKey="Wilschut, J" uniqKey="Wilschut J">J Wilschut</name></author><author><name sortKey="Frijlink, Hw" uniqKey="Frijlink H">HW Frijlink</name></author><author><name sortKey="Hinrichs, Wl" uniqKey="Hinrichs W">WL Hinrichs</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, D" uniqKey="Chen D">D Chen</name></author><author><name sortKey="Kristensen, D" uniqKey="Kristensen D">D Kristensen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, W" uniqKey="Wang W">W Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Anamur, C" uniqKey="Anamur C">C Anamur</name></author><author><name sortKey="Winter, G" uniqKey="Winter G">G Winter</name></author><author><name sortKey="Engert, J" uniqKey="Engert J">J Engert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kamerzell, Tj" uniqKey="Kamerzell T">TJ Kamerzell</name></author><author><name sortKey="Esfandiary, R" uniqKey="Esfandiary R">R Esfandiary</name></author><author><name sortKey="Joshi, Sb" uniqKey="Joshi S">SB Joshi</name></author><author><name sortKey="Middaugh, Cr" uniqKey="Middaugh C">CR Middaugh</name></author><author><name sortKey="Volkin, Db" uniqKey="Volkin D">DB Volkin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ohtake, S" uniqKey="Ohtake S">S Ohtake</name></author><author><name sortKey="Kita, Y" uniqKey="Kita Y">Y Kita</name></author><author><name sortKey="Arakawa, T" uniqKey="Arakawa T">T Arakawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pikal Cleland, Ka" uniqKey="Pikal Cleland K">KA Pikal-Cleland</name></author><author><name sortKey="Cleland, Jl" uniqKey="Cleland J">JL Cleland</name></author><author><name sortKey="Anchordoquy, Tj" uniqKey="Anchordoquy T">TJ Anchordoquy</name></author><author><name sortKey="Carpenter, Jf" uniqKey="Carpenter J">JF Carpenter</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Chang, L" uniqKey="Chang L">L Chang</name></author><author><name sortKey="Shepherd, D" uniqKey="Shepherd D">D Shepherd</name></author><author><name sortKey="Sun, J" uniqKey="Sun J">J Sun</name></author><author><name sortKey="Ouellette, D" uniqKey="Ouellette D">D Ouellette</name></author><author><name sortKey="Grant, Kl" uniqKey="Grant K">KL Grant</name></author><author><name sortKey="Tang, Xc" uniqKey="Tang X">XC Tang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kawai, K" uniqKey="Kawai K">K Kawai</name></author><author><name sortKey="Suzuki, T" uniqKey="Suzuki T">T Suzuki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chang, Bs" uniqKey="Chang B">BS Chang</name></author><author><name sortKey="Beauvais, Rm" uniqKey="Beauvais R">RM Beauvais</name></author><author><name sortKey="Dong, A" uniqKey="Dong A">A Dong</name></author><author><name sortKey="Carpenter, Jf" uniqKey="Carpenter J">JF Carpenter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carpenter, Jf" uniqKey="Carpenter J">JF Carpenter</name></author><author><name sortKey="Pikal, Mj" uniqKey="Pikal M">MJ Pikal</name></author><author><name sortKey="Chang, Bs" uniqKey="Chang B">BS Chang</name></author><author><name sortKey="Randolph, Tw" uniqKey="Randolph T">TW Randolph</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Amorij, Jp" uniqKey="Amorij J">JP Amorij</name></author><author><name sortKey="Meulenaar, J" uniqKey="Meulenaar J">J Meulenaar</name></author><author><name sortKey="Hinrichs, Wl" uniqKey="Hinrichs W">WL Hinrichs</name></author><author><name sortKey="Stegmann, T" uniqKey="Stegmann T">T Stegmann</name></author><author><name sortKey="Huckriede, A" uniqKey="Huckriede A">A Huckriede</name></author><author><name sortKey="Coenen, F" uniqKey="Coenen F">F Coenen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Maa, Yf" uniqKey="Maa Y">YF Maa</name></author><author><name sortKey="Ameri, M" uniqKey="Ameri M">M Ameri</name></author><author><name sortKey="Shu, C" uniqKey="Shu C">C Shu</name></author><author><name sortKey="Payne, Lg" uniqKey="Payne L">LG Payne</name></author><author><name sortKey="Chen, D" uniqKey="Chen D">D Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tang, Xc" uniqKey="Tang X">XC Tang</name></author><author><name sortKey="Pikal, Mj" uniqKey="Pikal M">MJ Pikal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Johnson, Re" uniqKey="Johnson R">RE Johnson</name></author><author><name sortKey="Kirchhoff, Cf" uniqKey="Kirchhoff C">CF Kirchhoff</name></author><author><name sortKey="Gaud, Ht" uniqKey="Gaud H">HT Gaud</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Armstrong, Tk" uniqKey="Armstrong T">TK Armstrong</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name></author><author><name sortKey="Patel, Mm" uniqKey="Patel M">MM Patel</name></author><author><name sortKey="Lentz, Yk" uniqKey="Lentz Y">YK Lentz</name></author><author><name sortKey="Anchordoquy, Tj" uniqKey="Anchordoquy T">TJ Anchordoquy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carpenter, Jf" uniqKey="Carpenter J">JF Carpenter</name></author><author><name sortKey="Crowe, Jh" uniqKey="Crowe J">JH Crowe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Allison, Sd" uniqKey="Allison S">SD Allison</name></author><author><name sortKey="Molina, Mdc" uniqKey="Molina M">MdC Molina</name></author><author><name sortKey="Anchordoquy, Tj" uniqKey="Anchordoquy T">TJ Anchordoquy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kasraian, K" uniqKey="Kasraian K">K Kasraian</name></author><author><name sortKey="Spitznagel, Tm" uniqKey="Spitznagel T">TM Spitznagel</name></author><author><name sortKey="Juneau, Ja" uniqKey="Juneau J">JA Juneau</name></author><author><name sortKey="Yim, K" uniqKey="Yim K">K Yim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chang, Bs" uniqKey="Chang B">BS Chang</name></author><author><name sortKey="Reeder, G" uniqKey="Reeder G">G Reeder</name></author><author><name sortKey="Carpenter, Jf" uniqKey="Carpenter J">JF Carpenter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, W" uniqKey="Liu W">W Liu</name></author><author><name sortKey="Wang, Dq" uniqKey="Wang D">DQ Wang</name></author><author><name sortKey="Nail, Sl" uniqKey="Nail S">SL Nail</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc 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pathogens</subject><subj-group><subject>Orthomyxoviruses</subject><subj-group><subject>Influenza viruses</subject><subj-group><subject>Influenza A virus</subject><subj-group><subject>H1N1</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject><subj-group><subject>Organisms</subject><subj-group><subject>Viruses</subject><subj-group><subject>Viral pathogens</subject><subj-group><subject>Orthomyxoviruses</subject><subj-group><subject>Influenza viruses</subject><subj-group><subject>Influenza A virus</subject><subj-group><subject>H1N1</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Physical Sciences</subject><subj-group><subject>Chemistry</subject><subj-group><subject>Chemical Compounds</subject><subj-group><subject>Organic Compounds</subject><subj-group><subject>Carbohydrates</subject><subj-group><subject>Disaccharides</subject><subj-group><subject>Sucrose</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Physical Sciences</subject><subj-group><subject>Chemistry</subject><subj-group><subject>Organic Chemistry</subject><subj-group><subject>Organic Compounds</subject><subj-group><subject>Carbohydrates</subject><subj-group><subject>Disaccharides</subject><subj-group><subject>Sucrose</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Physical Sciences</subject><subj-group><subject>Chemistry</subject><subj-group><subject>Chemical Compounds</subject><subj-group><subject>Organic Compounds</subject><subj-group><subject>Carbohydrates</subject><subj-group><subject>Disaccharides</subject><subj-group><subject>Trehalose</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Physical Sciences</subject><subj-group><subject>Chemistry</subject><subj-group><subject>Organic Chemistry</subject><subj-group><subject>Organic Compounds</subject><subj-group><subject>Carbohydrates</subject><subj-group><subject>Disaccharides</subject><subj-group><subject>Trehalose</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Immunology</subject><subj-group><subject>Vaccination and Immunization</subject><subj-group><subject>Vaccine Development</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Immunology</subject><subj-group><subject>Vaccination and Immunization</subject><subj-group><subject>Vaccine Development</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Public and Occupational Health</subject><subj-group><subject>Preventive Medicine</subject><subj-group><subject>Vaccination and Immunization</subject><subj-group><subject>Vaccine Development</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Zoology</subject><subj-group><subject>Animal Diseases</subject><subj-group><subject>Animal Influenza</subject><subj-group><subject>Swine Influenza</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Infectious Diseases</subject><subj-group><subject>Zoonoses</subject><subj-group><subject>Swine Influenza</subject></subj-group></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Development of a Freeze-Dried, Heat-Stable Influenza Subunit Vaccine Formulation</article-title><alt-title alt-title-type="running-head">Development of a Freeze-Dried, Heat-Stable Influenza Subunit Vaccine Formulation</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Flood</surname><given-names>Alexander</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Estrada</surname><given-names>Marcus</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>McAdams</surname><given-names>David</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Ji</surname><given-names>Yuhua</given-names></name><xref ref-type="aff" rid="aff002"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Dexiang</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="corresp" rid="cor001">*</xref></contrib></contrib-group><aff id="aff001"><label>1</label><addr-line>Devices and Tools Program, PATH, Seattle, Washington, United States of America</addr-line></aff><aff id="aff002"><label>2</label><addr-line>Drug Development Program, PATH, Seattle, Washington, United States of America</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Alsharifi</surname><given-names>Mohammed</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>University of Adelaide, AUSTRALIA</addr-line></aff><author-notes><fn fn-type="COI-statement" id="coi001"><p><bold>Competing Interests: </bold>We have the following interests. Novartis Pharmaceuticals (East Hanover, NJ) provided the generous supply of two lots of influenza H1N1 subunit bulk vaccine for this study. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.</p></fn><fn fn-type="con"><p><list list-type="simple"><list-item><p><bold>Conceptualization:</bold> DC AF.</p></list-item><list-item><p><bold>Data curation:</bold> DC AF ME DM YJ.</p></list-item><list-item><p><bold>Formal analysis:</bold> DC AF ME DM YJ.</p></list-item><list-item><p><bold>Funding acquisition:</bold> DC.</p></list-item><list-item><p><bold>Investigation:</bold> AF ME DM.</p></list-item><list-item><p><bold>Methodology:</bold> DC AF ME DM.</p></list-item><list-item><p><bold>Project administration:</bold> AF DC.</p></list-item><list-item><p><bold>Resources:</bold> AF ME.</p></list-item><list-item><p><bold>Supervision:</bold> DC.</p></list-item><list-item><p><bold>Validation:</bold> AF ME.</p></list-item><list-item><p><bold>Visualization:</bold> AF ME YJ.</p></list-item><list-item><p><bold>Writing – original draft:</bold> YJ ME.</p></list-item><list-item><p><bold>Writing – review & editing:</bold> DC DM.</p></list-item></list></p></fn><corresp id="cor001">* E-mail: <email>dchen@path.org</email></corresp></author-notes><pub-date pub-type="epub"><day>16</day><month>11</month><year>2016</year></pub-date><pub-date pub-type="collection"><year>2016</year></pub-date><volume>11</volume><issue>11</issue><elocation-id>e0164692</elocation-id><history><date date-type="received"><day>2</day><month>5</month><year>2016</year></date><date date-type="accepted"><day>29</day><month>9</month><year>2016</year></date></history><permissions><copyright-statement>© 2016 Flood et al</copyright-statement><copyright-year>2016</copyright-year><copyright-holder>Flood et al</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="pone.0164692.pdf"></self-uri><abstract><p>An influenza pandemic remains a major public health concern. A key strategy to prevent a pandemic is to stockpile and pre-position stable influenza vaccine to allow rapid deployment in response to an outbreak. However, most influenza vaccines today are formulated as liquids that are stable only within a temperature range of 2°C to 8°C and require use of a cold chain, making vaccine transportation, distribution, and storage complicated and expensive, particularly for developing countries. To support the National Strategy for Pandemic Influenza preparedness in the United States and internationally, we developed two lead dry formulations of stable H1N1 influenza subunit vaccines using freeze-drying technology. The stable formulations contain an excipient combination of a disaccharide, such as sucrose or trehalose, and glycine, in addition to a surfactant and phosphate buffer. The freeze-dried vaccines were shown to be safe and remained immunogenic in an in vivo study in mice. Moreover, the lead formulations demonstrated no significant loss of activity after 40 months at storage temperatures of 25°C and 37°C. This stability can be particularly attractive as it could eliminate the need to use a cold chain for vaccine deployment and facilitate integration of vaccine distribution with general drug distribution where appropriate. These freeze-dried thermostable influenza subunit vaccines could also reduce the frequency of vaccine stockpile turnover, offering a cost-effective option for pandemic preparedness.</p></abstract><funding-group><funding-statement>The authors received funding from the Biomedical Advanced Research and Development Authority (BARDA) for this work, under grant contract number HHSO1002011000040C (<ext-link ext-link-type="uri" xlink:href="http://www.phe.gov/about/BARDA/Pages/default.aspx">http://www.phe.gov/about/BARDA/Pages/default.aspx</ext-link>). Novartis Pharmaceuticals (East Hanover, NJ) provided the generous supply of two lots of influenza H1N1 subunit bulk vaccine. The funders had no role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><fig-count count="8"></fig-count><table-count count="4"></table-count><page-count count="18"></page-count></counts><custom-meta-group><custom-meta id="data-availability"><meta-name>Data Availability</meta-name><meta-value>Data are available from the stability studies and immunogenicity study, and can be accessed at: DOI <ext-link ext-link-type="uri" xlink:href="http://dx.doi.org/10.17605/OSF.IO/CFK8Z">10.17605/OSF.IO/CFK8Z</ext-link> or osf.io/dr4qu. The authors can be contacted at <email>dchen@path.org</email>.</meta-value></custom-meta></custom-meta-group></article-meta><notes><title>Data Availability</title><p>Data are available from the stability studies and immunogenicity study, and can be accessed at: DOI <ext-link ext-link-type="uri" xlink:href="http://dx.doi.org/10.17605/OSF.IO/CFK8Z">10.17605/OSF.IO/CFK8Z</ext-link> or osf.io/dr4qu. The authors can be contacted at <email>dchen@path.org</email>.</p></notes></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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