Antibodies and Congenital Neospora Caninum Transmission

描述：（由申请方提供）新孢子虫经胎盘传播 犬瘟热导致牛流产、死胎和先天性感染 还有狗 这种顶复门寄生虫类似于刚地弓形虫， 疟原虫属，这两种疾病都会导致流产和先天性感染， 人类 我们实验室以前的工作表明， 免疫力在预防由犬新孢子虫引起的流产中的作用，但 这种保护机制知之甚少。 本研究的目的 是确定抗体在预防先天性 传输 在寄生虫血症阶段，在初始感染之前， 胎盘或胎儿组织，抗体可以进入这个，否则 细胞内寄生虫 我们实验室的其他工作表明， 用整个速殖子抗原免疫诱导有害反应。 因此，诱导保护性应答的特异性抗原必须是 鉴定 寄生虫表面抗原对宿主细胞入侵是至关重要的， 是抗体中和的逻辑靶位点 体内寄生虫 本研究将研究SAG1，一种主要的表面蛋白 在N.犬，其在刚地弓形虫中的对应物已被证明是 与宿主细胞的附着和侵入有关。 SAG1抗体具有 已经显示出在体外阻断宿主细胞的侵入， 弓形虫 这一提议将检验新孢子虫上的表位 犬SAG1刺激中和抗体， 小鼠先天性传播并与防止流产相关 在牛中，具有以下特定目的： 具体目的1：确定含抗体的血清IgG是否转移至 SAG1在小鼠中抗议先天性寄生虫传播。 具体目标2：鉴定中和活性和SAG1拓扑 免疫血清中IgG的表位特异性，其保护免受N. caninum 先天性传染 具体目标3：确定血清抗体是否对中和敏感 表位与抗犬新孢子虫流产相关， 牛 这项建议的成功完成将是第一项研究， 抗体在抗细胞内原生动物新孢子虫中的作用 犬的 它还将直接解决免疫保护， 经胎盘传播的寄生虫，一种机制，可能是共同的， 其他顶复门原生动物。 该提案还将确定抗体， 表位将证明在保护性疫苗的开发中是无价的， 这是目前所有研究中最重要的方向， 犬新孢子虫 此外，该提案还研究了预防初始 滋养层细胞感染是顶复体的一个重要生物学机制 原生动物感染，如弓形虫病和疟原虫。

DESCRIPTION: (provided by applicant) Transplacental transmission of neospora caninum results in abortions, stillbirths, and congenital infection in cattle and dogs. This apicomplexan parasite is similar to Toxoplasma gondii and Plasmodium sp., both of which cause abortions and congenital infections in humans. Previous work in our laboratory indicates a role for maternal immunity in protection against abortions caused by Neospora caninum, but the mechanisms of that protection are poorly understood. The goal of this study is to identify the role of antibodies in protection against congenital transmission. During the parasitemic phase, prior to initial infection of placental or fetal tissues, antibodies could have access to this otherwise intracellular parasite. Other work from our laboratory indicates that immunization with whole tachyzoite antigens induces a harmful response. Therefore, specific antigens that induce a protective response must be identified. Parasite surface antigens are crucial to host cell invasion of apicomplexan protozoa and are a logical target site for antibody to neutralize parasites in vivo. This study will investigate SAG1, a major surface protein in N. caninum whose counterpart in Toxoplasma gondii has been shown to be involved with attachment and invasion of host cells. Antibodies to SAG1 have been shown to block invasion of host cells in vitro and both Neospora and Toxoplasma. This proposal will test the hypothesis that epitopes on Neospora caninum SAG1 stimulate neutralizing antibodies that are protective against congenital transmission in mice and correlate with protection against abortion in cattle with the following specific aims: Specific Aim 1: Determine if transfer of serum IgG containing antibodies to SAG1 protests against congenital parasite transmission in mice. Specific Aim 2: Identifying neutralizing activity and SAG1 topographical epitope specificity of IgG in immune serum that protects against N. caninum congential transmission. Specific Aim 3: Determine if serum antibodies to neutralization sensitive epitopes correlate with protection against Neospora caninum abortion in cattle. Successful completion of this proposal would be the first study to define the role of antibodies in the protection against intracellular protozoan Neospora caninum. It would also directly address immune protection against transplacental transmission of the parasite, a mechanism that may be common to other apicomplexan protozoa. The proposal would also identify antibodies and epitopes will prove invaluable in the development of a protective vaccine, which is currently the most important direction of any research involving Neospora caninum. In addition, the proposal studies prevention of initial infection of trophoblasts, a biologic mechanism critical to apicomplexan protozoan infections such as toxoplasmosis and plasmodium.