C-di-GMP with influenza vaccine showed enhanced and shifted immune responses in microneedle vaccination in the skin.

A microneedle is a biomedical device which consists of multiple micron scale needles. It is widely used in various fields to deliver drugs and vaccines to the skin effectively. However, when considering improved vaccine efficacy in microneedle vaccination, it is important to find an appropriate adjuvant that is able to be used in transdermal delivery. Herein, we demonstrated the applicability of c-di-GMP, which is a stimulator of interferon genes (STING) agonist, as an adjuvant for influenza microneedle vaccination. Thus, 2 and 10 μg of GMP with the influenza vaccine were coated onto a microneedle, and then, BALB/c mice were immunized with the coated microneedle to investigate the immunogenicity and protection efficacy of the influenza microneedle vaccination. As a result, the adjuvant groups had an enhanced IgG response, IgG subtypes and HI titer compared to the vaccine only group. In addition to the humoral immunity, the use of an adjuvant has also been shown to improve the cellular immune response. In a challenge study, adjuvant groups had a 100% survival rate and rapid weight recovery. Taken together, this study confirms that GMP is an effective adjuvant for influenza microneedle vaccination. Graphical abstract.