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

基本信息

批准号：
9210049
负责人：
RICHARD W COMPANS
金额：
$ 67.49万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
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/9210049
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 Elderly Exhibits FDA approved Goals Hospitalization Human Immune Immune response Immune system Immunity Immunization Immunologics Individual Infection Inflammatory Influenza Influenza A Virus, H1N1 Subtype Influenza A Virus, H7N9 Subtype Influenza vaccination Innate Immune System Intramuscular Morbidity - disease rate Mus Painless Phenotype Population Population Group Population Heterogeneity Public Health Recruitment Activity Research Risk Role Route Signal Transduction Site Skin Skin Aging Subunit Vaccines Support Groups T cell response Technology Up-Regulation Vaccination Vaccine Research Vaccines Virus Virus Diseases adaptive immune response aged aging population chemokine cytokine design experience global health group support high risk high risk population immunogenicity immunoregulation immunosenescence improved influenza outbreak influenza virus vaccine influenzavirus insight mortality mouse model nonhuman primate pandemic disease prevent public health relevance relative effectiveness senescence uptake vaccination strategy vaccine delivery vaccine development vaccine efficacy

项目摘要

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的高危人群，尽管目前的流感疫苗在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。在激发保护性免疫系统方面相对有效流感疫苗在成年人中的反应有限，但仅对年轻人和老年人产生有限的保护性免疫力。这些群体中效力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、缺乏事先接触和疫苗接种。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，从而限制了疫苗的应用。免疫系统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。数据和之前的研究，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，成功完成了这个项目，我们的发现激励我们，即皮肤微针输送现有 FDA 批准的流感疫苗配方可以增强效果。动物模型中的免疫反应并赋予改善因此，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。