IMMUNITY TO CHLAMYDIA ABORTUS

流产衣原体（Cab）是衣原体病或绵羊内源性流产和死产的病原体，对孕妇有人畜共患风险。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，并导致孕妇流产或死产。目前的1B减毒活疫苗可在接种疫苗的动物中引起疾病，而灭活疫苗仅具有微弱的保护作用。为了设计一种有效的疫苗，有必要了解能够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大小和质量与在自然感染后恢复的恢复期免疫个体中观察到的相似。我们提出这种疫苗将具有亚基设计，并通过CD4+、CD8+和γδ T细胞产生IFN-γ（和IL-17）来刺激强大的细胞介导的免疫反应。我们构建了一种重组霍乱弧菌鬼影（rVCG）疫苗，表达高度保守的Cab多态膜蛋白18D (Pmp18D)，在初步研究中产生了大量的生殖道免疫。本项目的目的是利用活的1B、rVCG亚单位疫苗和活的Cab感染来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导致疾病/病理。我们将比较接种基于rvgc的Pmp18D和减毒1B活疫苗以及衣原体活感染后疫苗和感染诱导免疫的强度和质量。目的1将研究小鼠免疫和感染后引起的功能性细胞和体液免疫的措施。我们将研究免疫或感染活衣原体后功能性细胞免疫（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分泌细胞频率[ASC]；免疫记忆）的几种测量方法。目的2将阐明CD4+、CD8+、γδ T细胞和抗体（Ab）在免疫或感染后保护性免疫中的作用，并研究TLR/NLRs和接头分子信号在感染和接种过程中的表达动态。

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.