IMMUNITY TO CHLAMYDIA ABORTUS

对流产衣原体的免疫力

• 批准号: 9197019
• 负责人: Francis O. Eko
• 金额: $ 43.33万
• 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/9197019
• 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; Genital system; Goals; Goat; Health; Humoral Immunities; Immune; Immune response; Immunity; Immunization; Immunoglobulin-Secreting Cells; Immunologic Memory; Inactivated Vaccines; Individual; Induced Abortion; Infection; Interferon Type II; Interleukin-17; Lead; Life; 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; T-Lymphocyte; Testing; Tissues; Vaccinated; Vaccination; Vaccines; Vibrio cholerae; Work; Zoonotic Infection; abortion; base; cell mediated immune response; cell transformation; cytokine; design; efficacy testing; enzootic; fetal; flu; immunogenic; interest; novel; pregnant; prevent; reproductive tract; stillbirth; transmission process; vaccine candidate; vaccine-induced immunity; vector

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胎的病原体，对孕妇构成人畜共患风险。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，孕妇流产或死胎。目前的1B减毒活疫苗在接种动物中引起疾病，灭活疫苗仅具有轻微的保护作用。为了设计有效的疫苗，有必要了解可以产生保护作用的免疫反应的性质。有人认为，由保护性疫苗引起的免疫应答的强度和质量将与从自然感染中恢复的恢复期免疫个体中观察到的相似。我们提出这样的疫苗将具有亚基设计，并通过由CD 4+、CD 8+和γδ T细胞产生IFN-γ（和IL-17）来刺激强烈和稳健的细胞介导的免疫应答。我们已经构建了一个重组霍乱弧菌鬼（rVCG）为基础的疫苗表达高度保守的Cab多态性膜蛋白18 D（Pmp 18 D），在初步研究中产生大量的生殖道免疫。本研究的目的是利用1B、rVCG亚单位活疫苗和Cab活感染，研究疫苗和感染诱导免疫的机制。我们假设Cab感染通过抑制宿主免疫而引起疾病/病理。我们将比较疫苗和感染诱导的免疫接种后的rVCG为基础的Pmp 18 D和减毒活1B疫苗，活衣原体感染的规模和质量。目的1研究免疫和感染后小鼠功能性细胞免疫和体液免疫的检测方法。我们将检查免疫或感染活衣原体后的功能性细胞免疫（Th 1/Th 2细胞因子产生水平; T细胞增殖/频率）和体液免疫（Ab水平，Ab分泌细胞[ASC]的频率;免疫记忆）的几项措施。目的2阐明CD 4+、CD 8+、γδ T细胞和抗体（Ab）在免疫或感染后保护性免疫中的作用，研究TLR/NLR和接头分子信号在感染和疫苗接种过程中的表达动态。