Long-term stability of influenza vaccine in a dissolving microneedle patch

• Type of Material: Article
• Authors: Matthew J. Mistilis, Georgia Institute of Technology; Jessica Joyce, Georgia Institute of Technology; E. Stein Esser, Emory University; Ioanna Skountzou, Emory University; Richard W Compans, Emory University; Andreas S. Bommarius, Georgia Institute of Technology; Mark R. Prausnitz, Emory University
• Language: English
• Date: 2017-04-01
• Publisher: Springer Verlag (Germany)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016, Controlled Release Society.
• Final Published Version (URL): http://dx.doi.org/10.1007/s13346-016-0282-2
• Title of Journal or Parent Work: Drug Delivery and Translational Research
• ISSN: 2190-393X
• Volume: 7
• Issue: 2
• Start Page: 195
• End Page: 205
• Grant/Funding Information: This work was supported in part by the National Institutes of Health.
• Keywords: TREHALOSE; WATER; Medicine, Research & Experimental; Pharmacology & Pharmacy; PRESERVATION; Microneedle; Influenza vaccine; Solid dosage form; SEASONAL INFLUENZA; PROTEIN STABILIZATION; Research & Experimental Medicine; Vaccine delivery; VIRUS-VACCINE; Science & Technology; GLASS-TRANSITION; Vaccine stability; Life Sciences & Biomedicine; Instruments & Instrumentation; Technology; DRUG-DELIVERY; Transdermal delivery; Vaccine formulation; COLD CHAIN; IMMUNOGENICITY
• Research Categories: Health Sciences, Immunology; Engineering, Biomedical; Biology, Microbiology

Abstract

This study tested the hypothesis that optimized microneedle patch formulations can stabilize trivalent subunit influenza vaccine during long-term storage outside the cold chain and when exposed to potential stresses found during manufacturing and storage. Formulations containing combinations of trehalose/sucrose, sucrose/arginine, and arginine/heptagluconate were successful at retaining most or all vaccine activity during storage at 25 °C for up to 24 months as determined by ELISA assay. The best formulation of microneedle patches contained arginine/heptagluconate, which showed no significant loss of vaccine activity during the study. To validate these in vitro findings, mice were immunized using trivalent influenza vaccine stored in microneedle patches for more than 1 year at 25 °C, which elicited antibody titers greater than or equal to fresh liquid vaccine delivered by intradermal injection, indicating the retention of immunogenicity during storage. Finally, influenza vaccine in microneedle patches lost no significant activity during exposure to 60 °C for 4 months, multiple freeze-thaw cycles, or electron beam irradiation. We conclude that optimally formulated microneedle patches can retain influenza vaccine activity during extended storage outside the cold chain and during other environmental stresses, which suggests the possibility of microneedle patch storage on pharmacy shelves without refrigeration.