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

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 one 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 four months, multiple freeze-thaw cycles, and 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.

Transdermal Protein Delivery Using Choline and Geranate (CAGE) Deep Eutectic Solvent

“…The formulation exhibited superior immune response compared to the same dose via intramuscular injection. [46][47][48] In addition, the same research group used these microneedles made using polyvinyl alcohol and sucrose to successfully deliver tetanus, rabies and ebola vaccines along with synthetic vaccines made of layer-by-layer microparticles against respiratory syncytial virus. [49][50][51][52] On the other hand, Donnelly et al used "super swelling" microneedles made of hydrogel forming polymers (Gantrez S-97, polyethylene glycol and Na 2 CO 3 ) to deliver 0.32 g OVA across the skin of Sprague Dawley rats.…”

A self-aggregating peptide: implications for the development of thermostable vaccine candidates

“…The use of biomaterials are a central part of novel strategies to develop next-generation vaccines [19,20], delivery systems [21,22] with improved thermostability [23].…”

Polymeric microneedles for transdermal protein delivery

“…A better understanding of the vaccine stability throughout the fabrication, storage and administration process is essential for the future optimization [94]. Appropriate formulation methods using MN patch preserve the long-term antigen immunogenicity and allow flexible storage conditions [95]. To assess the effect of the coating formulation to the stability of viral proteins, Zhu et al suspended the viral proteins in a coating solution and found the experimental responses were comparable with the control groups in terms of antibody production [96].…”