期刊
JOURNAL OF CONTROLLED RELEASE
卷 225, 期 -, 页码 192-204出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2016.01.019
关键词
Microneedle; Influenza vaccine; Broadly-neutralizing antibody; Stability; Virus vector vaccine
资金
- Science Foundation Ireland [NAP280]
- Enterprise Ireland [CF2011 1634]
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 6 months 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. (C) 2016 Elsevier B.V. All rights reserved.
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