Dissolving polymer microneedle patches for influenza vaccination : Nature Medicine : Nature Publishing Group

Nature Medicine | Technical Report

Dissolving polymer microneedle patches for influenza vaccination
Sean P Sullivan,Dimitrios G Koutsonanos,Maria del Pilar Martin,Jeong Woo Lee,Vladimir Zarnitsyn,Seong-O Choi,Niren Murthy,Richard W Compans,Ioanna Skountzou& Mark R Prausnitz

AffiliationsContributionsCorresponding authors Journal name:
Nature Medicine
Year published:
(2010)
DOI:
doi:10.1038/nm.2182
Received30 July 2009
Accepted23 April 2010
Published online18 July 2010
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.



Figures at a glance


leftFigure 1: Dissolving polymer microneedle patches.
(a) Side view of dissolving polymer microneedles. (b) Relative height of an array of microneedles next to a US nickel coin. (c) En face view of porcine cadaver skin after insertion and removal of microneedles, showing delivery of the encapsulated compound (sulforhodamine). (d) Fluorescence micrograph of pig skin histological section after insertion of dissolving microneedles ex vivo. (e) Brightfield micrograph of the same skin section with H&E staining.


Figure 2: Delivery to skin using microneedles.
(a) Polymer microneedle dissolution in pig skin ex vivo. Top, before insertion; middle, remaining polymer 1 min after insertion in skin; bottom, remaining polymer 5 min after insertion in skin. (b) Dissolving microneedle delivery efficiency to mice in vivo. Sulforhodamine was encapsulated within microneedles and administered to mice (n = 5 for each time point). The delivery efficiencies for the three time points were statistically different from one another (Student's t test, P < 0.05). (c) Effect of PVP and lyophilization on vaccine immunogenicity. Mice (n = 3) were immunized i.m. with 20 μg inactivated influenza virus (A/PR/8/34) that was either lyophilized or in solution with or without PVP added. Serum IgG antibody titers and HAI were measured 14 d after immunization. Unproc., unprocessed inactivated influenza virus in PBS; Lyo., lyophilized inactivated influenza virus redissolved in PBS; Unproc. + PVP, unprocessed inactivated influenza virus in PBS mixed with PVP; Lyo. + PVP, lyophilized inactivated influenza virus encapsulated in PVP; N, naïve mice. Error bars represent s.d. from three to five independent experiments.


Figure 3: Microneedle immunization studies.

These authors contributed equally to this work.
Sean P Sullivan & Dimitrios G Koutsonanos

Affiliations
Wallace H. Coulter Department of Biomedical Engineering at Emory University and Georgia Tech, Georgia Institute of Technology, Atlanta, Georgia, USA.
Sean P Sullivan,Niren Murthy &Mark R Prausnitz
Department of Microbiology & Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA.
Dimitrios G Koutsonanos,Maria del Pilar Martin,Richard W Compans &Ioanna Skountzou
School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
Jeong Woo Lee,Vladimir Zarnitsyn,Seong-O Choi &Mark R Prausnitz

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.

Competing financial 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.

Corresponding authors
Correspondence to:
Mark R Prausnitz (prausnitz@gatech.edu) or Ioanna Skountzou (iskount@emory.edu)

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Dissolving polymer microneedle patches for influenza vaccination : Nature Medicine : Nature Publishing Group