Microneedle delivery of an M2e-TLR5 ligand fusion protein to skin confers broadly cross-protective influenza immunity
Identifieur interne : 000457 ( Pmc/Checkpoint ); précédent : 000456; suivant : 000458Microneedle delivery of an M2e-TLR5 ligand fusion protein to skin confers broadly cross-protective influenza immunity
Auteurs : Bao-Zhong Wang [États-Unis] ; Harvinder S. Gill [États-Unis] ; Cheng He [République populaire de Chine] ; Changbo Ou [République populaire de Chine] ; Li Wang [États-Unis] ; Ying-Chun Wang [États-Unis] ; Hao Feng [États-Unis] ; Han Zhang [États-Unis] ; Mark R. Prausnitz [États-Unis] ; Richard W. Compans [États-Unis]Source :
- Journal of controlled release : official journal of the Controlled Release Society [ 0168-3659 ] ; 2014.
Abstract
Influenza vaccines with broad cross-protection are urgently needed to prevent an emerging influenza pandemic. A fusion protein of the TLR5-agonist domains from flagellin and multiple repeats of the conserved extracellular domain of the influenza matrix protein 2 (M2e) was constructed, purified and evaluated as such a vaccine. A painless vaccination method suitable for possible self-administration using coated microneedle arrays was investigated for skin-targeted delivery of the fusion protein in a mouse model. The results demonstrate that microneedle immunization induced strong humoral as well as mucosal antibody responses and conferred complete protection against homo- and heterosubtypic lethal virus challenges. Protective efficacy with microneedles was found to be significantly better than that seen with conventional intramuscular injection, and comparable to that observed with intranasal immunization. Because of its advantages for administration, safety and storage, microneedle delivery of M2e-flagellin fusion protein is a promising approach for an easy-to-administer universal influenza vaccine.
Url:
DOI: 10.1016/j.jconrel.2014.01.002
PubMed: 24417966
PubMed Central: 3951682
Affiliations:
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<front><div type="abstract" xml:lang="en"><p id="P1">Influenza vaccines with broad cross-protection are urgently needed to prevent an emerging influenza pandemic. A fusion protein of the TLR5-agonist domains from flagellin and multiple repeats of the conserved extracellular domain of the influenza matrix protein 2 (M2e) was constructed, purified and evaluated as such a vaccine. A painless vaccination method suitable for possible self-administration using coated microneedle arrays was investigated for skin-targeted delivery of the fusion protein in a mouse model. The results demonstrate that microneedle immunization induced strong humoral as well as mucosal antibody responses and conferred complete protection against homo- and heterosubtypic lethal virus challenges. Protective efficacy with microneedles was found to be significantly better than that seen with conventional intramuscular injection, and comparable to that observed with intranasal immunization. Because of its advantages for administration, safety and storage, microneedle delivery of M2e-flagellin fusion protein is a promising approach for an easy-to-administer universal influenza vaccine.</p>
</div>
</front>
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<front><journal-meta><journal-id journal-id-type="nlm-journal-id">8607908</journal-id>
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<title-group><article-title>Microneedle delivery of an M2e-TLR5 ligand fusion protein to skin confers broadly cross-protective influenza immunity</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Wang</surname>
<given-names>Bao-Zhong</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="corresp" rid="CR1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gill</surname>
<given-names>Harvinder S.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>He</surname>
<given-names>Cheng</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ou</surname>
<given-names>Changbo</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wang</surname>
<given-names>Li</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wang</surname>
<given-names>Ying-Chun</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Feng</surname>
<given-names>Hao</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhang</surname>
<given-names>Han</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Prausnitz</surname>
<given-names>Mark R.</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Compans</surname>
<given-names>Richard W.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="corresp" rid="CR1">*</xref>
</contrib>
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<aff id="A1"><label>1</label>
Department of Microbiology and Immunology, and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, 30322, United States of America</aff>
<aff id="A2"><label>2</label>
Department of Chemical Engineering, Texas Tech University, Lubbock, TX 79409-3121</aff>
<aff id="A3"><label>3</label>
Key Laboratory of Animal Epidemiology and Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing. 100094, China</aff>
<aff id="A4"><label>4</label>
School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, 30332, United States of America</aff>
<author-notes><corresp id="CR1"><label>*</label>
Corresponding authors: BZW, <email>bwang3@emory.edu</email>
, Phone: 404-712-1735, Fax: 404-727-3295; RWC, <email>rcompan@emory.edu</email>
, Phone: 404-727-2015; Fax: 404-727-8250.</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>14</day>
<month>2</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="epub"><day>11</day>
<month>1</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="ppub"><day>28</day>
<month>3</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>28</day>
<month>3</month>
<year>2015</year>
</pub-date>
<volume>178</volume>
<fpage>1</fpage>
<lpage>7</lpage>
<pmc-comment>elocation-id from pubmed: 10.1016/j.jconrel.2014.01.002</pmc-comment>
<permissions><copyright-statement>© 2013 Elsevier B.V. All rights reserved</copyright-statement>
<copyright-year>2013</copyright-year>
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<abstract><p id="P1">Influenza vaccines with broad cross-protection are urgently needed to prevent an emerging influenza pandemic. A fusion protein of the TLR5-agonist domains from flagellin and multiple repeats of the conserved extracellular domain of the influenza matrix protein 2 (M2e) was constructed, purified and evaluated as such a vaccine. A painless vaccination method suitable for possible self-administration using coated microneedle arrays was investigated for skin-targeted delivery of the fusion protein in a mouse model. The results demonstrate that microneedle immunization induced strong humoral as well as mucosal antibody responses and conferred complete protection against homo- and heterosubtypic lethal virus challenges. Protective efficacy with microneedles was found to be significantly better than that seen with conventional intramuscular injection, and comparable to that observed with intranasal immunization. Because of its advantages for administration, safety and storage, microneedle delivery of M2e-flagellin fusion protein is a promising approach for an easy-to-administer universal influenza vaccine.</p>
</abstract>
<kwd-group><kwd>Cross-protection</kwd>
<kwd>Influenza M2e</kwd>
<kwd>Microneedle array</kwd>
<kwd>TLR5 ligand</kwd>
<kwd>Universal influenza vaccine</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>République populaire de Chine</li>
<li>États-Unis</li>
</country>
<region><li>Texas</li>
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<name sortKey="Gill, Harvinder S" sort="Gill, Harvinder S" uniqKey="Gill H" first="Harvinder S." last="Gill">Harvinder S. Gill</name>
<name sortKey="Gill, Harvinder S" sort="Gill, Harvinder S" uniqKey="Gill H" first="Harvinder S." last="Gill">Harvinder S. Gill</name>
<name sortKey="Prausnitz, Mark R" sort="Prausnitz, Mark R" uniqKey="Prausnitz M" first="Mark R." last="Prausnitz">Mark R. Prausnitz</name>
<name sortKey="Wang, Li" sort="Wang, Li" uniqKey="Wang L" first="Li" last="Wang">Li Wang</name>
<name sortKey="Wang, Ying Chun" sort="Wang, Ying Chun" uniqKey="Wang Y" first="Ying-Chun" last="Wang">Ying-Chun Wang</name>
<name sortKey="Zhang, Han" sort="Zhang, Han" uniqKey="Zhang H" first="Han" last="Zhang">Han Zhang</name>
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<country name="République populaire de Chine"><noRegion><name sortKey="He, Cheng" sort="He, Cheng" uniqKey="He C" first="Cheng" last="He">Cheng He</name>
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<name sortKey="Ou, Changbo" sort="Ou, Changbo" uniqKey="Ou C" first="Changbo" last="Ou">Changbo Ou</name>
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