Enhanced immunity in intradermal vaccination by novel hollow microneedles

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The intradermal (<jats:styled-content style="fixed-case">ID</jats:styled-content>) route for vaccination represents an effective alternative to subcutaneous (<jats:styled-content style="fixed-case">SC</jats:styled-content>)/intramuscular administration to induce protective immunity. However, a critical issue associated with <jats:styled-content style="fixed-case">ID</jats:styled-content> vaccination is the precise delivery of solution in the upper dermis, which ensures enhanced immunity.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We fabricated a hollow microneedle unit made of poly‐glycolic acid by injection molding and bonding, and created a dedicated prototype injector. To ensure <jats:styled-content style="fixed-case">ID</jats:styled-content> delivery of solution, the injected site was macroscopically and microscopically examined. Serum immunoglobulin G antibody production was measured by enzyme immunoassay and compared in groups of rats following either <jats:styled-content style="fixed-case">ID</jats:styled-content> delivery with microneedles or <jats:styled-content style="fixed-case">SC</jats:styled-content> administration with a 27‐G stainless needle of graded vaccine doses.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The unit used a tandem array of six microneedles, each with a side delivery hole, and a conduit inside for solution. Microneedles installed in the injector punctured the skin with the aid of a spring. Injection of solution formed a wheal due to <jats:styled-content style="fixed-case">ID</jats:styled-content> distribution. Histologically, a wedge‐shaped skin defect in the upper skin corresponded to each puncture site. Antibody titers following vaccinations on days 1 and 8 were significantly higher with <jats:styled-content style="fixed-case">ID</jats:styled-content> injection than with <jats:styled-content style="fixed-case">SC</jats:styled-content> delivery on day 15 and every 7 days thereafter until day 36 with mumps vaccination, and until day 36 with varicella vaccination.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The microneedle unit presented here delivered solution intradermally without any difficulty and evoked antibody responses against viruses even with the reduced vaccine volume. Our findings confirm promising results of <jats:styled-content style="fixed-case">ID</jats:styled-content> delivery as an immunogenic option to enhance vaccination efficacy.</jats:p></jats:sec>