Targeting Dendritic Cell Subsets in Human Vagina to Elicit Local Immunity

靶向人类阴道中的树突状细胞亚群以引发局部免疫

基本信息

批准号：
7835184
负责人：
SangKon Oh
金额：
$ 49.99万
依托单位：
BAYLOR RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-29 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7835184
关键词：
Academic Medical Centers Address Adjuvant Antigen Targeting Antigen-Presenting Cells Antigens Area Autoimmunity B-Lymphocytes Bacteria Beds Biological Assay Biological Preservation CD8B1 gene Chlamydia Clinical Research Communicable Diseases Dendritic Cells Development Dose Employment Fc Receptor Female Flow Cytometry Funding Funding Opportunities Genital system Goals HIV Health Health Sciences Human Human Papillomavirus Humoral Immunities Hypersensitivity Immune response Immune system Immunity Immunohistochemistry Immunologic Surveillance Immunologist Immunology In Situ In Vitro Infection Institutes Knowledge Malignant Neoplasms Medicine Methods Molecular Morbidity - disease rate Mucosal Immunity Mucous Membrane Mus Occupations Physicians Prevention Preventive Public Health Research Route Scientist Secure Sexually Transmitted Diseases Simplexvirus Site Skin Software Engineering Surface System Systems Biology T-Lymphocyte Technology Testing Therapeutic Tissue Sample Tissues Training Translations Vaccination Vaccine Antigen Vaccines Vagina Work base burden of illness design in vivo insight meetings migration mortality mouse model mucosal vaccine multidisciplinary nonhuman primate novel novel strategies novel vaccines pathogen prevent programs public health relevance receptor response subcutaneous transmission process vaccine delivery vaccinology

项目摘要

DESCRIPTION (provided by applicant): This project addresses Broad Challenge Area 04-Clinical Research and Specific Challenge Topic 04-AI-101*- Develop novel methods and address key questions in mucosal immunology. Sexually transmitted diseases (STDs) cause high morbidity and mortality, and thus result in a major disease burden worldwide. New preventive vaccines against HPV have proven that protective immunity can be mounted; but challenges in curing HPV-associated cancer and other major STDs associated with HIV, HSV, Chlamydia, and other bacteria still remain. The female genital tract is a major infection site and a route for the transmission of pathogens. Therefore, vaccines that induce potent mucosal immunity in the vagina have a high potential for the prevention and treatment of STDs. The vagina is a promising site for mucosal vaccine administration. The key question is: how can we establish potent mucosal immunity against STDs in the vagina? Simply delivering vaccines to the vagina may not induce potent mucosal immunity. Dendritic cells (DCs) are major antigen presenting cells (APCs) for both cellular and humoral immunity, but different subsets of DCs have distinct functions in inducing and regulating immune responses. Thus, knowledge of the subsets of vaginal APCs will be crucial for designing mucosal vaccines that induce potent mucosal immunity in the vagina. However, the immunology of the human vagina is poorly understood. To fill the dual gaps of the lack of experts and limited knowledge, here we initiate a comprehensive study for harnessing the immunology of human vagina. This study is greatly facilitated by 1) procuring sufficient tissue samples from Baylor University Medical Center, 2) taking advantage of using the established knowledge in human skin DC subsets at the Baylor Institute for Immunology Research (BIIR), and 3) employing a systems biology approach for a comprehensive analysis of immune responses. At the end of this study, we will be able to provide knowledge in three key areas for developing mucosal vaccines against STDs: 1) The subsets of APCs that can elicit optimal quantity and quality of mucosal immunity in the vagina, 2) APC subset-specific surface receptors and activators for: a) delivering vaccines to appropriate subsets of APCs and b) activating the correct APC subsets, and 3) In situ experimental systems explored in this study will bring key insights of in vivo human immunology necessary for developing vaccines. At BIIR, we have developed a technology platform for targeting antigens directly to human DC subsets via anti-DC receptor antibody vehicles; and this work will permit informed decisions for choosing the targeting receptors and adjuvants best suited to elicit potent and sustained mucosal immunity. Importantly, this proposal fulfills the premises of the challenge funding opportunities by 1) developing novel methods and addressing key questions in human mucosal immunology, 2) generating a broad and major impact on health improvement worldwide by providing key knowledge for developing vaccines against a wide range of STD, 3) making a fundamental contribution in human immunology, and 4) preserving and creating jobs and training for highly skilled scientists. PUBLIC HEALTH RELEVANCE: This work will address the challenge in human mucosal immunology. It will have a broad impact in science and health as it will provide fundamental knowledge in the immunology of the human genital tract, particularly the vagina, which is a major site of infection and transmission of sexually-transmitted diseases (STDs). The results of this study will have immediate implications for the rational design and development of safe and effective vaccines against STDs. Importantly, this work will allow preservation and creation of jobs. 1

描述（由申请人提供）：该项目解决了广泛的挑战领域04-Clinical Research和特定挑战主题04-AI-101* - 开发新颖的方法并解决粘膜免疫学中的关键问题。性传播疾病（STD）导致高发病率和死亡率，因此在全球范围内导致重大疾病负担。针对HPV的新预防疫苗已经证明可以安装保护性免疫。但是，仍然存在与HIV，HSV，衣原体和其他细菌有关的治愈HPV相关癌症以及其他主要性病的挑战。女性生殖道是主要感染部位，也是病原体传播的途径。因此，在阴道中诱导有效的粘膜免疫的疫苗具有预防和治疗性病的高潜力。阴道是粘膜疫苗给药的有前途的部位。关键问题是：我们如何对阴道中的性病进行有效的粘膜免疫力？简单地向阴道输送疫苗可能不会诱导有效的粘膜免疫。树突状细胞（DC）是细胞和体液免疫的主要抗原呈递细胞（APC），但DC的不同子集在诱导和调节免疫反应方面具有不同的功能。因此，对阴道APC子集的知识对于设计诱导阴道中有效的粘膜免疫的粘膜疫苗至关重要。但是，人类阴道的免疫学知识鲜为人知。为了填补缺乏专家和有限知识的双重空白，在这里，我们启动了一项综合研究，以利用人类阴道的免疫学。 1）从贝勒大学医学中心（Baylor University Medical Center）获得足够的组织样本，2）利用贝勒免疫学研究所（BIIR）的人类皮肤DC亚群中的既定知识，以及3）采用系统生物学方法来全面分析免疫反应分析。在这项研究结束时，我们将能够在三个关键领域提供有关针对性质性质疾病的粘膜疫苗的知识：1）APC的子集可以引起阴道中最佳的粘膜免疫数量和粘膜免疫的质量和质量，2）APC亚集合特异性表面受体和激活因子和激活因子和激活因子，以：a）在以下方面向apc和apc的适当系统传递了apc的估算，并将APC的估算为apc，并在apc中估算了APC，该疫苗是APC的，APC的APC AISTES AISTIS AICTES AICTIS AICTES AICTIS AICTIS AISTIS AIVITS AIMISTISS AISTIS AIVESS INSTES传递给了APC，则是APC的APC，研究将带来开发疫苗所需的体内人类免疫学的关键见解。在BIIR，我们开发了一个技术平台，可通过抗DC受体抗体车直接靶向人类DC亚群。这项工作将允许明智的决定选择靶向受体和最适合于产生有效和持续的粘膜免疫力的佐剂。重要的是，该提案通过1）通过1）开发新方法并解决人类粘膜免疫学中的关键问题，2）通过提供针对广泛的STD的疫苗来为全球健康改善产生广泛而重大的影响，3）在人类免疫学方面提供基本的贡献，以及在人类免疫学方面做出基本贡献，以及4）培训和培训训练和培训。公共卫生相关性：这项工作将解决人类粘膜免疫学的挑战。它将在科学和健康中产生广泛的影响，因为它将提供人类生殖道免疫学的基本知识，尤其是阴道，这是性传播疾病（STD）的主要感染和传播部位。这项研究的结果将对针对性病的安全有效疫苗的合理设计和开发具有直接的影响。重要的是，这项工作将允许保存和创造工作。 1