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产的病原体，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类似流感的症状，并导致孕妇流产或死产。目前的减毒活疫苗 1B 会导致接种动物患病，而灭活疫苗只能起到有限的保护作用。为了设计有效的疫苗，有必要了解可产生保护作用的免疫反应的性质。有人认为，保护性疫苗引起的免疫反应的程度和质量与从自然感染中恢复的康复期免疫个体中观察到的免疫反应类似。我们建议这种疫苗将采用亚基设计，并通过 CD4+、CD8+ 和 γδ T 细胞产生 IFN-γ（和 IL-17）来刺激强大而有力的细胞介导的免疫反应。我们构建了一种基于重组霍乱弧菌菌影 (rVCG) 的疫苗，表达高度保守的 Cab 多态性膜蛋白 18D (Pmp18D)，在初步研究中该疫苗产生了显着的生殖道免疫力。该项目的目标是利用活1B、rVCG亚单位疫苗和活Cab感染来研究疫苗和感染诱导的免疫机制。我们假设 Cab 感染通过抑制宿主免疫力而导致疾病/病理。我们将比较使用基于 rVCG 的 Pmp18D 和减毒活疫苗 1B 疫苗以及活衣原体感染进行免疫后疫苗和感染诱导的免疫力的程度和质量。目标 1 将研究小鼠在免疫和感染后引发的功能性细胞和体液免疫的测量。我们将检查活衣原体免疫或感染后功能性细胞免疫（Th1/Th2 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] 频率；免疫记忆）的多项指标。目标 2 将阐明 CD4+、CD8+ 和 γδ T 细胞以及抗体 (Ab) 在免疫或感染后保护性免疫中的贡献，并研究感染和疫苗接种过程中 TLR/NLR 和接头分子信号传导的表达动态。