Vaccine efficacy of transcutaneous immunization with amyloid β using a dissolving microneedle array in a mouse model of Alzheimer's disease

• We examined vaccine efficacy of transcutaneous immunization for Alzheimer’s disease.
• Transcutaneous immunization using MicroHyala induced anti-Aβ1–42 immune responses.
• Our system may contribute to simple and easy-to-use vaccine for Alzheimer’s disease.

Vaccine therapy for Alzheimer's disease (AD) based on the amyloid cascade hypothesis has recently attracted attention for treating AD. Injectable immunization using amyloid β peptide (Aβ) comprising 1–42 amino-acid residues (Aβ1–42) as antigens showed therapeutic efficacy in mice; however, the clinical trial of this injected Aβ1–42 vaccine was stopped due to the incidence of meningoencephalitis caused by excess activation of Th1 cells infiltrating the brain as a serious adverse reaction. Because recent studies have suggested that transcutaneous immunization (TCI) is likely to elicit Th2-dominant immune responses, TCI is expected to be effective in treating AD without inducing adverse reactions. Previously reported TCI procedures employed complicated and impractical vaccination procedures; therefore, a simple, easy-to-use, and novel TCI approach needs to be established. In this study, we investigated the vaccine efficacy of an Aβ1–42-containing TCI using our novel dissolving microneedle array (MicroHyala; MH) against AD. MH-based TCI induced anti-Aβ1–42 immune responses by simple and low-invasive application of Aβ1–42-containing MH to the skin. Unfortunately, this TCI system resulted in little significant improvement in cognitive function and Th2-dominant immune responses, suggesting the need for further modification.

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