Skin Vaccination Against Influenza in the Young And Aged

 描述(由申请人提供)：人们普遍认为，年轻人和老年人是感染流感病毒的高危人群。在这些人群中，流感相关疾病和继发性并发症的发病率和死亡率最高。尽管目前的流感疫苗在诱导保护性免疫方面相对有效 在成年人的反应中，它们只对年轻人和老年人提供有限的保护性免疫。在这些群体中，效力降低的原因可能是各种因素的结果，包括裂解和亚单位流感疫苗效力/免疫原性降低，年轻人缺乏事先接触和免疫系统不成熟的情况，以及老年人观察到的免疫衰老。目前用于接种这些疫苗的肌肉内途径也可能不太有效地摄取和呈递抗原，因为与MHC II免疫细胞的相互作用减少，从而限制了免疫反应的大小。为了提高这些高危人群的疫苗效力，我们建议确定与肌肉免疫相比，通过年轻人和老年人的皮肤接种流感疫苗是否可以提供更好的免疫反应和保护。我们计划以我们的初步数据和之前的研究为基础，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来成功完成这个项目。我们的发现是，与年轻人和老年人肌肉免疫相比，皮肤微针注射现有FDA批准的流感疫苗配方可以增强动物模型的免疫反应，并提供更好的保护。因此，我们的研究有可能提出新的疫苗接种方法和免疫战略，这些方法和免疫战略将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.