Antigen Presentation and Pulmonary Immunity to Plague

抗原呈递和肺对鼠疫的免疫力

• 批准号: 7009628
• 负责人: Steven W. Dow
• 金额: $ 44.21万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-15 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7009628
• 关键词: T lymphocyte; Yersinia pestis disease; antibody specificity; antigen antibody reaction; antigen presentation; biotechnology; cellular immunity; confocal scanning microscopy; cooperative study; cytotoxic T lymphocyte; drug administration routes; enzyme linked immunosorbent assay; flow cytometry; fluorescent dye /probe; humoral immunity; immunologic memory; immunomagnetic separation; intermolecular interaction; laboratory mouse; liposomes; lung; mucosal immunity; nucleic acids; scintillation counter; vaccine development; viral vaccines

DESCRIPTION (provided by applicant): The overall goal of this project is to develop a novel mucosal vaccine for generating rapid and effective pulmonary immunity against aerosolized Yersinia pestis. These studies will focus on a novel vaccine delivery system that consists of liposome-antigen-nucleic acid complexes (LANAC). Our preliminary studies indicate that LANAC vaccines can elicit marked and long-lived T cell responses against both peptide and protein antigens, with an efficiency that in most cases exceeds that elicited by viral-vectored or dendritic cell vaccines. Moreover, preliminary data also indicate that LANAC vaccines can elicit marked intrapulmonary immunity and humoral immunity and are effective after mucosal administration. The ability to elicit strong cellular immunity may be particularly useful for control of Yersinia within infected macrophages. Therefore, the objectives of this proposal are to define the immunological mechanisms by which liposome-nucleic acid complexes enhance antigen presentation and to determine whether mucosal LANAC vaccines formulated with either Yersinia protein or peptide antigens can elicit protective immunity against aerosol challenge with Yersinia. The specific aims of this project are to (1) determine how liposomes and nucleic acids interact to enhance antigen presentation; (2) identify critical antigen-presenting cell targets for LANAC and how mucosal routes of immunization affect antigen presentation; (3) determine whether mucosal or parenteral vaccination with recombinant Yersinia F1 or V antigens can elicit protective immunity to aerosol challenge; (4) determine whether small secreted peptides from Yersinia can elicit protective CTL responses. These studies have relevance to the stated objectives of this RFA because they will yield important mechanistic information on a novel vaccine adjuvant for use in immunization against plague and other Category A-C agents. In addition, this project will provide critical proof-of-principal validation of the LANAC vaccine approach and the ability to elicit rapid pulmonary immunity against inhaled Yersinia, particularly after mucosal immunization.

描述（由申请人提供）： 该项目的总体目标是开发一种新型粘膜疫苗，以产生针对雾化鼠疫耶尔森氏菌的快速有效的肺部免疫。这些研究将重点关注由脂质体-抗原-核酸复合物（LANAC）组成的新型疫苗递送系统。我们的初步研究表明，LANAC 疫苗可以针对肽和蛋白质抗原引发显着且持久的 T 细胞反应，其效率在大多数情况下超过病毒载体疫苗或树突状细胞疫苗所引发的效率。此外，初步数据还表明，LANAC疫苗可引发显着的肺内免疫和体液免疫，且粘膜给药后有效。 引发强大的细胞免疫的能力对于控制受感染的巨噬细胞内的耶尔森氏菌可能特别有用。因此，本提案的目的是确定脂质体-核酸复合物增强抗原呈递的免疫学机制，并确定用耶尔森氏菌蛋白或肽抗原配制的粘膜 LANAC 疫苗是否可以引发针对耶尔森氏菌气溶胶攻击的保护性免疫。该项目的具体目标是（1）确定脂质体和核酸如何相互作用以增强抗原呈递； (2) 确定 LANAC 的关键抗原呈递细胞靶标以及粘膜免疫途径如何影响抗原呈递； (3)确定用重组耶尔森氏菌F1或V抗原进行粘膜或肠胃外疫苗接种是否可以引发对气溶胶攻击的保护性免疫； (4)确定耶尔森氏菌的小分泌肽是否可以引发保护性CTL反应。这些研究与本次 RFA 的既定目标相关，因为它们将产生有关用于鼠疫和其他 A-C 类疫苗免疫的新型疫苗佐剂的重要机制信息。此外，该项目将为 LANAC 疫苗方法和引发针对吸入耶尔森氏菌的快速肺部免疫的能力提供关键的原理验证，特别是在粘膜免疫后。