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

Bao Zhong Wang, Harvinder S. Gill, Cheng He, Changbo Ou, Li Wang, Ying Chun Wang, Hao Feng, Han Zhang, Mark R. Prausnitz, Richard W. Compans

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Influenza vaccines with broad cross-protection are urgently needed to prevent an emerging influenza pandemic. A fusion protein of the Toll-like receptor (TLR) 5-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.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalJournal of Controlled Release
Volume178
Issue number1
DOIs
StatePublished - Mar 28 2014

Keywords

  • Cross-protection
  • Influenza M2e
  • Microneedle array
  • TLR5 ligand
  • Universal influenza vaccine

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