Enhanced immunity in intradermal vaccination by novel hollow microneedles.

BACKGROUND: The intradermal (ID) route for vaccination represents an effective alternative to subcutaneous (SC)/intramuscular administration to induce protective immunity. However, a critical issue associated with ID vaccination is the precise delivery of solution in the upper dermis, which ensures enhanced immunity. METHODS: We fabricated a hollow microneedle unit made of poly-glycolic acid by injection molding and bonding, and created a dedicated prototype injector. To ensure ID 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 ID delivery with microneedles or SC administration with a 27-G stainless needle of graded vaccine doses. RESULTS: 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 ID 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 ID injection than with SC delivery on day 15 and every 7 days thereafter until day 36 with mumps vaccination, and until day 36 with varicella vaccination. CONCLUSIONS: 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 ID delivery as an immunogenic option to enhance vaccination efficacy.

Performance of ultrafiltration membrane process combined with coagulation/sedimentation.

Effects of coagulation/sedimentation as a pre-treatment on the dead-end ultrafiltration (UF) membrane process were studied in terms of membrane fouling and removal efficiency of natural dissolved organic matter, using Chitose River water. Two types of experiment were carried out. One was a bench scale membrane filtration with jar-test and the other was membrane filtration pilot plant combined with the Jet Mixed Separator (JMS) as a pre-coagulation/sedimentation unit. In the bench scale experiment, the effects of coagulant dosage, pH and membrane operating pressure on the membrane fouling and removal efficiency of natural dissolved organic matter were investigated. In the pilot plant experiment, we also investigated the effect of pre-coagulation/sedimentation on the membrane fouling and the removal efficiency of natural dissolved organic matter. Coagulation/sedimentation prior to membrane filtration process controlled the membrane fouling and increased the removal efficiency of natural dissolved organic matter.