About this item:

241 Views | 291 Downloads

Author Notes:

Corresponding author. iskount@emory.edu

We thank Nadia Lelutiu for her scientific feedback and editing of this manuscript, Dahnide Taylor-Williams for technical support, and Kiran Gill and David Lee for Emory Vaccine Center core facility expertise with flow cytometry and Luminex assays, respectively.

M.R.P. is an inventor of patents licensed to companies developing microneedle-based products, is a paid advisor to companies developing microneedle-based products and is a founder/shareholder of companies developing microneedle-based products (e.g., Micron Biomedical).

E.Q.L, L.K.M., E.S.E., E.V.V, J.T.B., S.W., J.P.P., N.B., F.K. R.W.C, I.S. declare that they have no conflicts of interest.

This potential conflict of interest has been disclosed and is managed by Georgia Tech and Emory University.

Subjects:

Research Funding:

This work was supported by NIH grant 5R01AI111557.

Keywords:

  • Science & Technology
  • Physical Sciences
  • Life Sciences & Biomedicine
  • Chemistry, Multidisciplinary
  • Pharmacology & Pharmacy
  • Chemistry
  • GM-CSF
  • Microneedle
  • Influenza
  • Adjuvant
  • Skin
  • Co-delivery
  • COLONY-STIMULATING FACTOR
  • PROTECTIVE IMMUNE-RESPONSES
  • T-CELL RESPONSES
  • DENDRITIC CELLS
  • VIRUS INFECTION
  • DRUG-DELIVERY
  • IMMUNOGENICITY
  • IMMUNIZATION
  • EXPRESSION
  • ADJUVANT

Stable incorporation of GM-CSF into dissolvable microneedle patch improves skin vaccination against influenza

Show all authors Show less authors

Tools:

Journal Title:

Journal of Controlled Release

Volume:

Volume 276

Publisher:

, Pages 1-16

Type of Work:

Article | Post-print: After Peer Review

Abstract:

The widely used influenza subunit vaccine would benefit from increased protection rates in vulnerable populations. Skin immunization by microneedle (MN) patch can increase vaccine immunogenicity, as well as increase vaccination coverage due to simplified administration. To further increase immunogenicity, we used granulocyte-macrophage colony stimulating factor (GM-CSF), an immunomodulatory cytokine already approved for skin cancer therapy and cancer support treatment. GM-CSF has been shown to be upregulated in skin following MN insertion. The GM-CSF-adjuvanted vaccine induced robust and long-lived antibody responses cross-reactive to homosubtypic and heterosubtypic influenza viruses. Addition of GM-CSF resulted in increased memory B cell persistence relative to groups given influenza vaccine alone and led to rapid lung viral clearance following lethal infection with homologous virus in the mouse model. Here we demonstrate that successful incorporation of the thermolabile cytokine GM-CSF into MN resulted in improved vaccine-induced protective immunity holding promise as a novel approach to improved influenza vaccination. To our knowledge, this is the first successful incorporation of a cytokine adjuvant into dissolvable MNs, thus advancing and diversifying the rapidly developing field of MN vaccination technology.

Copyright information:

© 2018 The Authors.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Creative Commons License

Export to EndNote