Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Technical Report
  • Published:

Dissolving polymer microneedle patches for influenza vaccination


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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

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.

Similar content being viewed by others


  1. Centers for Disease Control and Prevention. Influenza activity—United States and worldwide, 2007–08 season. MMWR Morb. Mortal. Wkly. Rep. 57, 692–697 (2008).

  2. Prausnitz, M.R., Mikszta, J.A., Cormier, M. & Andrianov, A.K. Microneedle-based vaccines. Curr. Top. Microbiol. Immunol. 333, 369–393 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Glenn, G.M. & Kenney, R.T. Mass vaccination: solutions in the skin. Curr. Top. Microbiol. Immunol. 304, 247–268 (2006).

    CAS  PubMed  Google Scholar 

  4. Belshe, R.B. et al. Serum antibody responses after intradermal vaccination against influenza. N. Engl. J. Med. 351, 2286–2294 (2004).

    Article  CAS  PubMed  Google Scholar 

  5. Holland, D. et al. Intradermal influenza vaccine administered using a new microinjection system produces superior immunogenicity in elderly adults: a randomized controlled trial. J. Infect. Dis. 198, 650–658 (2008).

    Article  PubMed  Google Scholar 

  6. Van Damme, P. et al. Safety and efficacy of a novel microneedle device for dose sparing intradermal influenza vaccination in healthy adults. Vaccine 27, 454–459 (2009).

    Article  PubMed  Google Scholar 

  7. Hickling, J. & Jones, R. Intradermal Delivery of Vaccines: A Review of the Literature and the Potential for Development for Use in Low- and Middle-Income Countries. (Program for Appropriate Technology in Health, Ferney Voltaire, France, 2009).

    Google Scholar 

  8. Flynn, P.M. et al. Influence of needle gauge in Mantoux skin testing. Chest 106, 1463–1465 (1994).

    Article  CAS  PubMed  Google Scholar 

  9. Prausnitz, M.R. & Langer, R. Transdermal drug delivery. Nat. Biotechnol. 26, 1261–1268 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gill, H.S., Denson, D.D., Burris, B.A. & Prausnitz, M.R. Effect of microneedle design on pain in human volunteers. Clin. J. Pain 24, 585–594 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Mikszta, J.A. et al. Improved genetic immunization via micromechanical disruption of skin-barrier function and targeted epidermal delivery. Nat. Med. 8, 415–419 (2002).

    Article  CAS  PubMed  Google Scholar 

  12. Widera, G. et al. Effect of delivery parameters on immunization to ovalbumin following intracutaneous administration by a coated microneedle array patch system. Vaccine 24, 1653–1664 (2006).

    Article  CAS  PubMed  Google Scholar 

  13. Koutsonanos, D.G. et al. Transdermal influenza immunization with vaccine-coated microneedle arrays. PLoS One 4, e4773 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Zhu, Q. et al. Immunization by vaccine-coated microneedle arrays protects against lethal influenza virus challenge. Proc. Natl. Acad. Sci. USA 106, 7968–7973 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kim, Y.C. et al. Enhanced memory responses to seasonal H1N1 influenza vaccination of the skin with the use of vaccine-coated microneedles. J. Infect. Dis. 201, 190–198 (2010).

    Article  CAS  PubMed  Google Scholar 

  16. Miyano, T. et al. Sugar micro needles as transdermic drug delivery system. Biomed. Microdevices 7, 185–188 (2005).

    Article  CAS  PubMed  Google Scholar 

  17. Ito, Y., Yoshimitsu, J., Shiroyama, K., Sugioka, N. & Takada, K. Self-dissolving microneedles for the percutaneous absorption of EPO in mice. J. Drug Target. 14, 255–261 (2006).

    Article  CAS  PubMed  Google Scholar 

  18. Lee, J.W., Park, J.H. & Prausnitz, M.R. Dissolving microneedles for transdermal drug delivery. Biomaterials 29, 2113–2124 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sullivan, S.P., Murthy, N. & Prausnitz, M.R. Minimally invasive protein delivery with rapidly dissolving microneedles. Adv. Mater. 20, 933–938 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Robinson, B.V. PVP: A Critical Review of the Kinetics and Toxicology of Polyvinylpyrrolidone (Povidone). (Lewis Publishers, Chelsea, Michigan, 1990).

    Google Scholar 

  21. Park, J.-H., Allen, M.G. & Prausnitz, M.R. Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery. J. Control. Release 104, 51–66 (2005).

    Article  CAS  PubMed  Google Scholar 

  22. Bronaugh, R.L., Stewart, R.F. & Congdon, E.R. Methods for in vitro percutaneous absorption studies II. Animal models for human skin. Toxicol. Appl. Pharmacol. 62, 481–488 (1982).

    Article  CAS  PubMed  Google Scholar 

  23. McGill, J. & Legge, K.L. Cutting edge: contribution of lung-resident T cell proliferation to the overall magnitude of the antigen-specific CD8 T cell response in the lungs following murine influenza virus infection. J. Immunol. 183, 4177–4181 (2009).

    Article  CAS  PubMed  Google Scholar 

  24. Strengell, M., Sareneva, T., Foster, D., Julkunen, I. & Matikainen, S. IL-21 up-regulates the expression of genes associated with innate immunity and TH1 response. J. Immunol. 169, 3600–3605 (2002).

    Article  PubMed  Google Scholar 

  25. Ozaki, K. et al. A critical role for IL-21 in regulating immunoglobulin production. Science 298, 1630–1634 (2002).

    Article  CAS  PubMed  Google Scholar 

  26. Zeng, R. et al. Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function. J. Exp. Med. 201, 139–148 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Miller, M.A. & Pisani, E. The cost of unsafe injections. Bull. World Health Organ. 77, 808–811 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Mitragotri, S. Immunization without needles. Nat. Rev. Immunol. 5, 905–916 (2005).

    Article  CAS  PubMed  Google Scholar 

  29. Ravin, H.A., Seligman, A.M. & Fine, J. Polyvinyl pyrrolidone as a plasma expander; studies on its excretion, distribution and metabolism. N. Engl. J. Med. 247, 921–929 (1952).

    Article  CAS  PubMed  Google Scholar 

  30. Doherty, P.C. & Kelso, A. Toward a broadly protective influenza vaccine. J. Clin. Invest. 118, 3273–3275 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Katsikis, P.D., Schoenberger, S.P. & Pulendran, B. Probing the 'labyrinth' linking the innate and adaptive immune systems. Nat. Immunol. 8, 899–901 (2007).

    Article  CAS  PubMed  Google Scholar 

  32. Kupper, T.S. & Fuhlbrigge, R.C. Immune surveillance in the skin: mechanisms and clinical consequences. Nat. Rev. Immunol. 4, 211–222 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Miller, L.S. & Modlin, R.L. Toll-like receptors in the skin. Semin. Immunopathol. 29, 15–26 (2007).

    Article  CAS  PubMed  Google Scholar 

  34. Skountzou, I., Quan, F.S., Jacob, J., Compans, R.W. & Kang, S.M. Transcutaneous immunization with inactivated influenza virus induces protective immune responses. Vaccine 24, 6110–6119 (2006).

    Article  CAS  PubMed  Google Scholar 

  35. Amorij, J.P. et al. Rational design of an influenza subunit vaccine powder with sugar glass technology: preventing conformational changes of haemagglutinin during freezing and freeze-drying. Vaccine 25, 6447–6457 (2007).

    Article  CAS  PubMed  Google Scholar 

  36. Compans, R.W. Hemagglutination-inhibition: rapid assay for neuraminic acid-containing viruses. J. Virol. 14, 1307–1309 (1974).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Reed, L.J. & Muench, H. A simple method of estimating fifty per cent endpoints. Am. J. Hyg. 27, 493–497 (1938).

    Google Scholar 

Download references


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.

Author information

Authors and Affiliations



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.

Ethics declarations

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.

Supplementary information

Supplementary Text and Figures

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

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sullivan, S., Koutsonanos, D., del Pilar Martin, M. et al. Dissolving polymer microneedle patches for influenza vaccination. Nat Med 16, 915–920 (2010).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing