Induction of broad immunity by thermostabilised vaccines incorporated in dissolvable microneedles using novel fabrication methods

• Published in: Journal of controlled release Vol. 225; pp. 192 - 204
• Main Authors: Vrdoljak, Anto, Allen, Evin A., Ferrara, Francesca, Temperton, Nigel J., Crean, Abina M., Moore, Anne C.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10.03.2016
• Subjects: Adenoviridae; Adenovirus; Animals; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Broadly-neutralizing antibody; Dimethylpolysiloxanes; Drug Delivery Systems; Drug Stability; Female; Hemagglutination Inhibition Tests; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Immunoglobulin G - blood; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H3N2 Subtype - immunology; Influenza vaccine; Influenza Vaccines - administration & dosage; Mice, Inbred BALB C; Microinjections; Microneedle; Needles; Silicon; Solubility; Stability; Vaccination - instrumentation; Vaccination - methods; Vaccines, Inactivated; Vaccinia virus; Virus vector vaccine; Virus vector vaccine; Stability; Broadly-neutralizing antibody; Influenza vaccine; Microneedle
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2016.01.019

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°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. Precisely dispensing formulation onto microneedle moulds permits the production of heterogeneous patches without wasted material. Influenza vaccine-loaded microneedle patches induce broader neutralizing antibody responses compared to intramuscular injection. [Display omitted]