PandemieGrippaleV1, Main, Exploration, bibRecordById, PMC:3951682

Microneedle delivery of an M2e-TLR5 ligand fusion protein to skin confers broadly cross-protective influenza immunity

Identifieur interne : 000E28 ( Main/Exploration ); précédent : 000E27; suivant : 000E29

Microneedle 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.

RBID : PMC:3951682

Descripteurs français

English descriptors

KwdEn :
- Administration, Cutaneous, Animals, Cell Line, Dogs, Flagellin (administration & dosage), Flagellin (immunology), Immunity, Immunoglobulin G (blood), Immunoglobulin G (immunology), Influenza A Virus, H1N1 Subtype (immunology), Influenza A Virus, H3N2 Subtype (immunology), Influenza Vaccines (administration & dosage), Ligands, Madin Darby Canine Kidney Cells, Mice, Microinjections, Needles, Orthomyxoviridae Infections (blood), Orthomyxoviridae Infections (immunology), Orthomyxoviridae Infections (prevention & control), Orthomyxoviridae Infections (virology), Recombinant Fusion Proteins (administration & dosage), Recombinant Fusion Proteins (immunology), Toll-Like Receptor 5 (chemistry), Toll-Like Receptor 5 (immunology), Viral Matrix Proteins (administration & dosage), Viral Matrix Proteins (immunology).
MESH :
- chemical , administration & dosage : Flagellin, Influenza Vaccines, Recombinant Fusion Proteins, Viral Matrix Proteins.
- chemical , blood : Immunoglobulin G.
- chemical , chemistry : Toll-Like Receptor 5.
- chemical , immunology : Flagellin, Immunoglobulin G, Recombinant Fusion Proteins, Toll-Like Receptor 5, Viral Matrix Proteins.
- blood : Orthomyxoviridae Infections.
- immunology : Influenza A Virus, H1N1 Subtype, Influenza A Virus, H3N2 Subtype, Orthomyxoviridae Infections.
- prevention & control : Orthomyxoviridae Infections.
- virology : Orthomyxoviridae Infections.
- Administration, Cutaneous, Animals, Cell Line, Dogs, Immunity, Ligands, Madin Darby Canine Kidney Cells, Mice, Microinjections, Needles.

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:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951682

DOI: 10.1016/j.jconrel.2014.01.002
PubMed: 24417966
PubMed Central: 3951682

Affiliations:

Le document en format XML

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<term>Chiens</term>
<term>Immunité</term>
<term>Infections à Orthomyxoviridae</term>
<term>Ligands</term>
<term>Lignée cellulaire</term>
<term>Microinjections</term>
<term>Récepteur de type Toll-5</term>
<term>Souris</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<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>
</TEI>
<affiliations><list><country><li>République populaire de Chine</li>
<li>États-Unis</li>
</country>
<region><li>Texas</li>
</region>
</list>
<tree><country name="États-Unis"><noRegion><name sortKey="Wang, Bao Zhong" sort="Wang, Bao Zhong" uniqKey="Wang B" first="Bao-Zhong" last="Wang">Bao-Zhong Wang</name>
</noRegion>
<name sortKey="Compans, Richard W" sort="Compans, Richard W" uniqKey="Compans R" first="Richard W." last="Compans">Richard W. Compans</name>
<name sortKey="Feng, Hao" sort="Feng, Hao" uniqKey="Feng H" first="Hao" last="Feng">Hao Feng</name>
<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>
</country>
<country name="République populaire de Chine"><noRegion><name sortKey="He, Cheng" sort="He, Cheng" uniqKey="He C" first="Cheng" last="He">Cheng He</name>
</noRegion>
<name sortKey="Ou, Changbo" sort="Ou, Changbo" uniqKey="Ou C" first="Changbo" last="Ou">Changbo Ou</name>
</country>
</tree>
</affiliations>
</record>

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Microneedle delivery of an M2e-TLR5 ligand fusion protein to skin confers broadly cross-protective influenza immunity

Microneedle delivery of an M2e-TLR5 ligand fusion protein to skin confers broadly cross-protective influenza immunity

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