Induction of broad immunity by thermostabilised vaccines incorporated in dissolvable microneedles using novel fabrication methods
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Date
2016-03
Authors
Vrdoljak, Anto
Allen, Evin A.
Ferrara, Francesca
Temperton, Nigel J.
Crean, Abina M.
Moore, Anne C.
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Published Version
Abstract
Dissolvable microneedle (DMN) patches for immunization have multiple benefits, including vaccine stability and ease-of-use. However, conventional DMN fabrication methods have several drawbacks. Here we describe a novel, microfluidic, drop dispensing-based dissolvable microneedle production method that overcomes these issues. Uniquely, heterogeneous arrays, consisting of microneedles of diverse composition, can be easily produced on the same patch. Robustness of the process was demonstrated by incorporating and stabilizing adenovirus and MVA vaccines. Clinically-available trivalent inactivated influenza vaccine (TIV) in DMN patches is fully stable for greater than 6months at 40 degrees C. Immunization using low dose TIV-loaded DMN patches induced significantly higher antibody responses compared to intramuscular-based immunization in mice. TIV-loaded patches also induced a broader, heterosubtypic neutralizing antibody response. By addressing issues that will be faced in large-scale fill-finish DMN fabrication processes and demonstrating superior thermostable characteristics and immunogenicity, this study progresses the translation of this microneedle platform to eventual clinical deployment.
Description
Keywords
Broadly-neutralizing antibody , Influenza vaccine , Microneedle , Stability , Virus vector vaccine
Citation
Vrdoljak, A., Allen, E. A., Ferrara, F., Temperton, N. J., Crean, A. M. and Moore, A. C. (2016) 'Induction of broad immunity by thermostabilised vaccines incorporated in dissolvable microneedles using novel fabrication methods', Journal of Controlled Release, 225, pp. 192-204. doi: 10.1016/j.jconrel.2016.01.019