Stability Kinetics of Influenza Vaccine Coated onto Microneedles During Drying and Storage

Abstract

Purpose This study sought to determine the effects of microneedle coating formulation, drying time and storage time on antigen stability and in vivo immunogenicity of influenza microneedle vaccines. Methods The stability of inactivated influenza virus vaccine was monitored by hemagglutination (HA) activity and virus particle aggregation as a function of storage time and temperature with or without trehalose. In vivo immunogenicity of inactivated influenza vaccines coated onto microneedles was determined in mice by virus-specific antibody titers and survival rates. Results In the absence of trehalose, HA activity decreased below 10% and to almost zero after 1 h and 1 month of drying, respectively. Addition of trehalose maintained HA activity above 60% after drying and above 20% after 1 month storage at 25°C. Loss of HA activity generally correlated with increased virus particle aggregation. Administration of microneedles coated with trehalose-stabilized influenza vaccine yielded high serum IgG antibody titers even after 1 month storage, and all animals survived with minimal weight loss after lethal challenge infection. Conclusions Inactivated influenza virus vaccine coated on microneedles with trehalose significantly improved the HA activity as well as in vivo immunogenicity of the vaccine after an extended time of storage.

Microneedle patch delivery to the skin of virus-like particles containing heterologous M2e extracellular domains of influenza virus induces broad heterosubtypic cross-protection

“…In contrast to liquid formulation, a number of different carbohydrate excipients were tested as stabilizers for pharmaceutical vaccine compounds during the formulation of a dry powder and trehalose was found to be most effective [39]. The addition of trehalose prevented physical changes in secondary and tertiary structure of influenza HA protein during a freezing process [40-41] and significantly improved the stability of influenza VLPs [23, 37]. MN coating with influenza M2e5x VLPs involves a drying process that accompanies a change of vaccine formulation from liquid to solid.…”

Microneedles: an emerging transdermal drug delivery system

“…These challenges can be overcome by use of microneedles. Highly hydrophilic drug formulations like PEGylated naltrexone or hydrophobic formulations of drugs like ketoprofen, show a many-fold increase in area under the curve (AUC) and maximum drug concentration [58][59][60] Coat and poke Adjuvant increases cellular immunogenicity, safety and self life. Hepatitis B vaccine [61] Poke and release Antigenicity was maintained at high temperature.…”

Carboxymethylcellulose–Chitosan‐coated microneedles with modulated hydration properties

“…7,8 To alleviate these issues, storage at a reduced water vapor pressure 9 and the use of various excipients, such as sucrose or trehalose, have been considered essential for stabilizing and controlling the water sensitivity of drug or vaccine formulations. 10,11 In this study, we explored the potential of polyelectrolyte complexes, which can be formed on the surface of hydrophilic formulations in a microfabrication process, to modulate the hydration properties of microneedles. To this end, sodium carboxymethylcellulose (CMC; Fig.…”