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

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 degrees 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.