IMMUNITY TO CHLAMYDIA ABORTUS

对流产衣原体的免疫力

• 批准号: 9321388
• 负责人: Francis O. Eko
• 金额: $ 43.71万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-26 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9321388
• 关键词: Adjuvant; Adoptive Transfer; Adult; Animals; Antibodies; Antigens; Attenuated; Attenuated Vaccines; CD8B1 gene; Cattle; Cells; Cellular Immunity; Child; Chlamydia; Chlamydia Infections; Country; Cytolysis; Development; Disease; Economics; Family suidae; Frequencies; Genes; Goals; Goat; Humoral Immunities; Immune; Immune response; Immunity; Immunization; Immunoglobulin-Secreting Cells; Immunologic Memory; Inactivated Vaccines; Individual; Induced Abortion; Infection; Interferon Type II; Interleukin-17; Lead; Livestock; Location; Measures; Membrane Proteins; Modeling; Monitor; Mus; N-terminal; Nature; Open Reading Frames; Outcome; Pathology; Plasmids; Preclinical Testing; Pregnant Women; Premature Labor; Prevention; Production; Recombinants; Risk; Serologic tests; Sheep; Signaling Molecule; Subunit Vaccines; Symptoms; System; Systemic infection; T-Cell Proliferation; Testing; Tissues; Vaccinated; Vaccination; Vaccines; Vibrio cholerae; Work; Zoonoses; abortion; base; cell mediated immune response; cell transformation; cytokine; design; efficacy testing; enzootic; fetal; flu; genital infection; immunogenic; interest; novel; pregnant; prevent; public health relevance; reproductive tract; stillbirth; transmission process; vaccine candidate; vaccine-induced immunity; vector; γδ T cells

Chlamydia abortus (Cab), the causative agent of chlamydiosis or ovine enzootic abortion and stillbirth, poses a zoonotic risk to pregnant women. Zoonotic infections are frequently asymptomatic leading to development of flu-like symptoms in both children and adults and abortion or stillbirth in pregnant women. Current live attenuated 1B vaccines cause disease in vaccinated animals and inactivated vaccines are only marginally protective. In order to design an effective vaccine, it is necessary to understand the nature of the immune response that can lead to protection. It has been suggested that the magnitude and quality of the immune response elicited by a protective vaccine would be similar to that observed in convalescent, immune individuals that have recovered from a natural infection. We propose such a vaccine will have a subunit design and stimulate strong and robust cell-mediated immune responses via the production of IFN-γ (and IL-17) by CD4+, CD8+ and γδ T cells. We have constructed a recombinant Vibrio cholerae ghost (rVCG)-based vaccine expressing the highly conserved Cab polymorphic membrane protein 18D (Pmp18D), which in preliminary studies generated substantial genital tract immunity. The goal of this project is to utilize the live 1B, rVCG subunit vaccine and live Cab infection to investigate the mechanisms of vaccine- and infection-induced immunity. We hypothesize that Cab infection causes disease/pathology by suppressing host immunity. We will compare the magnitude and quality of vaccine- and infection-induced immunity following immunization with the rVCG-based Pmp18D and live attenuated 1B vaccines, and live Chlamydia infection. Aim 1 will investigate measures of functional cellular and humoral immunity elicited in mice following immunization and infection. We will examine several measures of functional cellular immunity (levels of Th1/Th2 cytokine production; T cell proliferation/frequency) and humoral immunity (Ab levels, frequency of Ab secreting cells [ASC]; immunological memory) after immunization or infection with live Chlamydia. Aim 2 will elucidate the contributions of CD4+, CD8+ and γδ T cells, and antibody (Ab) in protective immunity after immunization or infection and investigate the expression dynamics of TLR/NLRs and adaptor molecule signaling during infection and vaccination.

流产衣原体(Cab)是衣原体病或羊地方性流产和死产的病原体，对孕妇构成人畜共患病的风险。人畜共患感染通常无症状，导致儿童和成人出现流感样症状，孕妇流产或死产。目前的减毒活1B疫苗会在接种的动物中引起疾病，灭活疫苗只能起到轻微的保护作用。为了设计一种有效的疫苗，有必要了解可导致保护的免疫反应的性质。有人提出，保护性疫苗引起的免疫反应的大小和质量与在从自然感染中恢复的恢复期免疫个体中观察到的相似。我们认为这样的疫苗将有一个亚单位设计，并通过产生干扰素-γ(和IL-17)由CD_4~+、CD_8~+和γδT细胞刺激强大的细胞介导的免疫反应。我们构建了一种基于霍乱弧菌幽灵(RVCG)的重组疫苗，表达高度保守的Cab多态膜蛋白18D(Pmp18D)，在初步研究中可产生大量的生殖道免疫。本项目的目标是利用1B、rVCG亚单位活疫苗和Cab活感染来研究疫苗和感染诱导免疫的机制。我们推测Cab感染通过抑制宿主免疫而引起疾病/病理。我们将比较基于rVCG的Pmp18D疫苗和减毒1B活疫苗免疫后疫苗和感染诱导免疫的数量和质量，以及活的衣原体感染。目的1研究免疫和感染后小鼠细胞免疫和体液免疫的功能指标。我们将检测免疫或感染衣原体后的细胞免疫功能(Th1/Th2细胞因子水平；T细胞增殖/频率)和体液免疫(抗体水平、抗体分泌细胞频率[ASC]；免疫记忆)的几项指标。目的2阐明T细胞亚群CD_4~+、CD_8~+、γδ~+T细胞及抗体在免疫或感染后保护性免疫中的作用，并探讨TLR/NLR在感染和免疫过程中的表达动态及接头分子信号转导途径。