Skin Vaccination Against Influenza in the Young And Aged

年轻人和老年人的流感皮肤疫苗接种

• 批准号: 8886505
• 负责人: RICHARD W COMPANS
• 金额: $ 70.29万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-06 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8886505
• 关键词: Adult; Animal Model; Animals; Antigen-Presenting Cells; Antigens; Attenuated Live Virus Vaccine; B-Lymphocytes; Cavia; Cells; Cessation of life; Characteristics; Child; Data; Effectiveness; Elderly; Environment; Exhibits; FDA approved; Goals; Hospitalization; Human; Immune; Immune response; Immune system; Immunity; Immunization; Individual; Infection; Inflammatory; Influenza; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H7N9 Subtype; Influenza vaccination; Intramuscular; Morbidity - disease rate; Mus; Population; Population Group; Population Heterogeneity; Public Health; Regulation; Relative (related person); Research; Risk; Role; Route; Signal Transduction; Site; Skin; Skin Aging; Subunit Vaccines; T cell response; Technology; Up-Regulation; Vaccination; Vaccine Research; Vaccines; Virus; Virus Diseases; adaptive immunity; aged; chemokine; cytokine; design; experience; global health; group support; high risk; immunogenicity; immunosenescence; improved; influenza outbreak; influenza virus vaccine; influenzavirus; insight; mortality; mouse model; nonhuman primate; pandemic disease; prevent; public health relevance; senescence; uptake; vaccination strategy; vaccine delivery; vaccine development; vaccine efficacy

 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.

 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高风险的两个人群。这些人群中流感相关疾病和继发并发症的发病率和死亡率最高。尽管目前的流感疫苗在引发保护性免疫方面相对有效 成年人的反应，它们只赋予年轻人和老年人有限的保护性免疫力。这些群体中功效降低的原因可能是多种因素造成的，包括裂解疫苗和亚单位流感疫苗的效力/免疫原性降低、缺乏事先接触、在年轻人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。由于与 MHC II 免疫细胞的相互作用减少，目前用于施用这些疫苗的肌肉注射途径对于抗原的摄取和呈递也可能不太有效，从而限制了免疫反应的强度。为了提高这些高危人群的疫苗功效，我们建议确定与肌肉注射免疫相比，通过年轻人和老年人的皮肤注射流感疫苗是否可以改善免疫反应和保护。我们计划以我们的初步数据和之前的研究为基础，并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，成功完成这个项目。我们的研究结果激励我们，即与年轻人和老年人的肌肉注射免疫相比，皮肤微针注射现有 FDA 批准的流感疫苗制剂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策略，从而影响和改善全球公共卫生。