Influenza immunization with trehalose-stabilized virus-like particle vaccine using microneedles

Abstract

Morbidity and mortality due to seasonal and pandemic influenza could be reduced by simpler vaccination methods that enable improved vaccination coverage. In this study, solid metal microneedles coated with influenza virus-like particle (VLP) vaccine were inserted into skin for intradermal immunization. Microneedles were applied to the skin by hand and designed for simple administration with little or no training. Inclusion of trehalose in the coating formulation significantly increased vaccine stability during coating by maintaining hemagglutination activity. Mice vaccinated with stabilized microneedles developed strong antibody responses comparable to conventional intramuscular vaccination and were fully protected against subsequent viral challenge. Whereas, coating microneedles with a coating solution lacking trehalose led to only partial protection against lethal viral challenge. Therefore, our results show that microneedles coated with trehalose-stabilized VLP vaccine can be a promising tool for improving influenza vaccination.

Figure 1

Effect of trehalose on the kinetics of HA activity loss by VLPs coated onto microneedles. VLPs were coated (●) without and (▽) with 15% trehalose present in the coating formulation. HA activity was measured at different times to assess antigenicity. (A) Short-term and (B) long-term kinetics of HA activity loss (SCS: standard coating solution, T: trehalose).

Figure 2

Induction of antibody response and protection against viral challenge after vaccination. (A) Total serum antibody responses specific to influenza virus (IgG) measured 2 and 4 weeks after immunization with either microneedles coated with VLP vaccine or intramuscular injection of the same VLP vaccine (+: p<0.05 compared to MN, ^: p<0.05 compared to MN+T, *: p<0.05 compared to IM). (B) Body weight change of immunized mice after lethal challenge infection. (MN: microneedles without trehalose, MN+T: microneedles with trehalose, IM: intramuscular injection of reconstituted vaccine without trehalose, IM+T: intramuscular injection of reconstituted vaccine with trehalose, Naive: no treatment.)