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.

真正的Enzootic堕胎和仍然生日的衣原体Abortus（CAB）对孕妇构成了人畜共患的风险。人畜共患感染通常是不对称的，导致儿童和成人的流感样症状以及孕妇的流产或生日。当前的活死1B疫苗导致疫苗接种的动物疾病，而被灭活的疫苗仅受到少量保护。为了设计有效的疫苗，有必要了解可以导致保护的免疫激发的性质。有人提出，受保护的疫苗引起的免疫激素的大小和质量与从自然感染中恢复过的营务中观察到的相似。我们提出这种疫苗将具有亚基设计，并通过CD4+，CD8+和γδT细胞的IFN-γ（和IL-17）的产生来刺激强大而鲁棒的细胞介导的免疫响应。我们已经构建了一种基于高度组成的CAB多态性膜蛋白18D（PMP18D）的重组弧菌霍乱幽灵（RVCG）的疫苗，该疫苗在初步研究中产生了实质性的生殖道免疫史。该项目的目的是利用LIVE 1B，RVCG亚基疫苗和Live CAB感染来研究疫苗和感染引起的免疫史的机制。我们假设CAB感染通过抑制宿主免疫来引起疾病/病理。我们将与基于RVCG的PMP18D免疫后的疫苗和感染诱导的免疫力的大小和质量，并实时衰减1B疫苗，以及实时的衣原体感染。 AIM 1将研究免疫和感染后在小鼠中引起的功能性细胞和体液免疫学的测量。我们将研究功能性细胞免疫学（TH1/Th2细胞因子的水平； T细胞增殖/频率）和体液免疫学（AB水平，AB分泌细胞的频率[ASC]；免疫学记忆）或感染了活着的chamydia后。 AIM 2将阐明免疫抑制或感染后CD4+，CD8+和γδT细胞以及保护性免疫学中的抗体（AB），并研究在感染和疫苗接种期间TLR/NLR和衔接分子信号传导的表达动力学。