title: Induction of broad immunity by thermostabilised vaccines incorporated in dissolvable microneedles using novel fabrication methods.
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°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.
authors.affiliation: School of Pharmacy, University College Cork, Cork, Ireland.
authors.forename: Anto
authors.initials: A
authors.lastname: Vrdoljak
authors.affiliation: School of Pharmacy, University College Cork, Cork, Ireland.
authors.forename: Evin A
authors.initials: EA
authors.lastname: Allen
authors.affiliation: School of Pharmacy, University of Kent, the Medway, UK.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferrara
authors.affiliation: School of Pharmacy, University of Kent, the Medway, UK.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Temperton
authors.affiliation: School of Pharmacy, University College Cork, Cork, Ireland.
authors.forename: Abina M
authors.initials: AM
authors.lastname: Crean
authors.affiliation: School of Pharmacy, University College Cork, Cork, Ireland; Department of Pharmacology, University College Cork, Cork, Ireland. Electronic address: anne.moore@ucc.ie.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Moore
mesh_terms: D000256:Adenoviridae; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D004129:Dimethylpolysiloxanes; D016503:Drug Delivery Systems; D004355:Drug Stability; D005260:Female; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage*; D008807:Mice, Inbred BALB C; D008845:Microinjections; D009339:Needles; D012825:Silicon; D012995:Solubility; D014611:Vaccination / Q000295:instrumentation / Q000379:methods; D015164:Vaccines, Inactivated; D014616:Vaccinia virus
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004129:Dimethylpolysiloxanes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; C013830:baysilon; D012825:Silicon
keywords: Broadly-neutralizing antibody; Influenza vaccine; Microneedle; Stability; Virus vector vaccine