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Dissolving polymer microneedle patches for influenza vaccination

Abstract

Influenza prophylaxis would benefit from a vaccination method enabling simplified logistics and improved immunogenicity without the dangers posed by hypodermic needles. Here we introduce dissolving microneedle patches for influenza vaccination using a simple patch-based system that targets delivery to skin's antigen-presenting cells. Microneedles were fabricated using a biocompatible polymer encapsulating inactivated influenza virus vaccine for insertion and dissolution in the skin within minutes. Microneedle vaccination generated robust antibody and cellular immune responses in mice that provided complete protection against lethal challenge. Compared to conventional intramuscular injection, microneedle vaccination resulted in more efficient lung virus clearance and enhanced cellular recall responses after challenge. These results suggest that dissolving microneedle patches can provide a new technology for simpler and safer vaccination with improved immunogenicity that could facilitate increased vaccination coverage.

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Figure 1: Dissolving polymer microneedle patches.
Figure 2: Delivery to skin using microneedles.
Figure 3: Microneedle immunization studies.
Figure 4: Long-lived immune responses.
Figure 5: Cellular immune responses after challenge.

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Acknowledgements

This study was carried out at the Emory Vaccine Center and the Georgia Tech Center for Drug Design, Development and Delivery and Institute for Bioengineering and Biosciences. The work was supported in part by US National Institutes of Health grants R01-EB006369 and U01-AI084579 and contract HHSN266200700006C. S.P.S. was a trainee supported by a fellowship from the US Department of Education Graduate Assistance in Areas of National Need program. M.d.P.M. was a trainee supported by contract HHSN266200700006C from the US National Institutes of Health–National Institute of Allergy and Infectious Diseases.

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Authors

Contributions

S.P.S., D.G.K., M.d.P.M. and I.S. carried out most experimental studies; J.W.L. and V.Z. prepared microneedles and helped generate the Supplementary Data; S.-O.C. prepared the molds used to fabricate microneedles; S.P.S., D.G.K., I.S. and M.R.P. designed the study and its analysis; S.P.S., I.S. and M.R.P. wrote the manuscript; and N.M., R.W.C., I.S. and M.R.P. supervised the project.

Corresponding authors

Correspondence to Ioanna Skountzou or Mark R Prausnitz.

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Competing interests

M.R.P. serves as a consultant to and is an inventor on patents licensed to companies developing microneedle-based products. This possible conflict of interest is being managed by Georgia Tech and Emory University.

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Supplementary Data, Supplementary Figures 1–3 and Supplementary Methods (PDF 192 kb)

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Sullivan, S., Koutsonanos, D., del Pilar Martin, M. et al. Dissolving polymer microneedle patches for influenza vaccination. Nat Med 16, 915–920 (2010). https://doi.org/10.1038/nm.2182

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