The safety and immunogenicity of inactivated rotavirus vaccine delivered by a dissolving microneedle patch in rats

The development of dissolving microneedle patches (dMNPs) for inactivated rotavirus vaccine (IRV) requires concurrent evaluation of safety parameters, including local and systemic toxicity and immune response characteristics. The aim of this study is to evaluate the toxicological safety profiles and immunogenic potential of IRV dMNPs in rats through assessment of systemic toxicity, local responses, and neutralizing activities. IRV dMNPs were examined for stability under different storage conditions (5 ± 3°C and 25 ± 2°C) for up to 24 months. Toxicology assessment included clinical observation, body weight monitoring, food consumption, hematology, clinical chemistry, organ weight analysis, and histopathological examination. Local tolerance was evaluated using Draize scoring and microscopic examination of the administration sites. Immunogenicity was evaluated by measuring neutralizing activities in sera against homotypic and heterotypic RV strains. The potency of IRV dMNPs was found stable for at least 24 months at 5 ± 3°C, and for 12 months at 25 ± 2°C. Toxicological evaluation showed no adverse systemic effects, with all clinical pathology parameters remaining within normal ranges. Local dermal reactions were mild (mean Draize scores <1.5) and subsided within 48 h. Histopathology showed only low to mild inflammatory changes at the application sites, with complete resolution by the end of study (day 57). Immunological analysis showed robust and cross-reactive neutralizing activities against homotypic and heterotypic RV strains in sera of rats. IRV dMNPs showed strong stability and an excellent safety profile while also inducing robust and extensive immune responses, supporting its further development as an alternate IRV platform.