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J Control Release. 2014 Jan 11. pii: S0168-3659(14)00019-4. doi: 10.1016/j.jconrel.2014.01.002. [Epub ahead of print]
Microneedle delivery of an M2e-TLR5 ligand fusion protein to skin confers broadly cross-protective influenza immunity.
Wang BZ1, Gill HS2, He C3, Ou C3, Wang L4, Wang YC4, Feng H4, Zhang H4, Prausnitz MR5, Compans RW6.
Author information
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.
Copyright ? 2014. Published by Elsevier B.V.
KEYWORDS:
Cross-protection, Influenza M2e, Microneedle array, TLR5 ligand, Universal influenza vaccine
PMID:
24417966
[PubMed - as supplied by publisher]
Microneedle delivery of an M2e-TLR5 ligand fusion protein to skin confers broadly cross-protective influenza immunity.
Wang BZ1, Gill HS2, He C3, Ou C3, Wang L4, Wang YC4, Feng H4, Zhang H4, Prausnitz MR5, Compans RW6.
Author information
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.
Copyright ? 2014. Published by Elsevier B.V.
KEYWORDS:
Cross-protection, Influenza M2e, Microneedle array, TLR5 ligand, Universal influenza vaccine
PMID:
24417966
[PubMed - as supplied by publisher]
