Skin Vaccination Against Influenza in the Young And Aged

 描述（由申请人提供）：人们普遍认为，年轻人和老年人是流感病毒感染的两个高风险人群。这些人群中流感相关疾病和继发性并发症的发病率和死亡率最高。虽然目前的流感疫苗在诱导保护性免疫方面相对有效， 尽管它们在成人中产生了免疫应答，但它们只能在年轻人和老年人中提供有限的保护性免疫。这些人群中疗效降低的原因可能是多种因素造成的，包括裂解和亚单位流感疫苗的效力/免疫原性降低、缺乏既往暴露和在年轻个体中观察到的免疫系统不成熟以及在老年人中观察到的免疫衰老。目前用于施用这些疫苗的肌内途径也可能由于与MHC II免疫细胞的相互作用减少而对抗原摄取和呈递不太有效，从而限制了免疫应答的幅度。为了提高疫苗在这些高危人群中的效力，我们建议确定与肌内免疫相比，通过年轻人和老年人的皮肤接种流感疫苗是否可以提高免疫应答和保护。我们计划在我们的初步数据和先前研究的基础上，利用我们在不同类型的微针设计和技术以及独特的动物模型方面的丰富经验，成功完成该项目。我们的动机是我们的发现，即皮肤微针递送现有FDA批准的流感疫苗制剂可以增强动物模型中的免疫应答，并在年轻人和老年人中与肌内免疫相比提供更好的保护。因此，我们的研究有可能提出新的疫苗接种方法和免疫策略，从而影响和改善全球公共卫生。

 DESCRIPTION (provided by applicant): It is widely recognized that the young and elderly represent two population groups at high risk from influenza virus infection. Morbidity and mortality from influenza-related illness and secondary complications are highest in these groups. Although current influenza vaccines are relatively effective in eliciting protective immune responses in adults, they only confer limited protective immunity in the young and aged. The reasons for the reduced efficacy in these groups could be a result of various factors including reduced potency/immunogenicity of split and subunit influenza vaccines, the lack of prior exposure and immaturity of the immune system observed in young individuals and the immunosenescence observed in the elderly. The current intramuscular route used to administer these vaccines may also be less effective for antigen uptake and presentation due to the reduced interaction with MHC II immune cells, thus limiting the magnitude of the immune responses. In order to improve vaccine efficacy in these high risk groups we propose to determine if delivery of influenza vaccine through the skin of the young and aged can confer improved immune responses and protection when compared to intramuscular immunization. We plan to build on our preliminary data and previous studies, and take advantage of our extensive experience with different types of microneedle designs and technologies and unique animal models to successfully complete this project. We are motivated by our findings that skin microneedle delivery of existing FDA-approved influenza vaccine formulations can enhance the immune responses in animal models and confer improved protection when compared to intramuscular immunization in the young and aged. Thus, our research has the potential to suggest new vaccination approaches and immunization strategies that will impact and improve public health globally.