Antibodies and Congenital Neospora Caninum Transmission

描述：(申请人提供)新孢子菌经胎盘传播 犬病会导致牛流产、死产和先天性感染。 还有狗。这种顶端复合体寄生虫类似于弓形虫和 疟原虫，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，母体的作用 对犬新孢子虫引起的流产具有免疫力，但 人们对这种保护机制知之甚少。这项研究的目的是 是为了确定抗体在预防先天性心脏病中的作用 变速箱。在寄生虫流行阶段，在首次感染之前 胎盘或胎儿组织，否则抗体可能会接触到它 胞内寄生虫。我们实验室的其他工作表明 用速殖子全抗原免疫会引起有害反应。 因此，诱导保护性反应的特定抗原必须是 已确认身份。寄生虫表面抗原对宿主细胞的入侵至关重要 顶端复合体原虫，是抗体中和的合理靶点 体内的寄生虫。这项研究将对主要的表面蛋白SAG1进行研究 在犬弓形虫中，其对应的弓形虫已被证明是 与宿主细胞的附着和入侵有关。抗SAG1抗体有 已被证明在体外可以阻止宿主细胞的入侵，新孢子菌和 弓形虫。这项提议将检验新孢子菌表位的假设 犬类SAG1刺激中和抗体，以防止 小鼠的先天性传播及其与流产保护的关系 在具有以下特定目的的牛身上： 具体目标1：确定血清中含有抗体的免疫球蛋白是否转移到 SAG1抗议先天性寄生虫在小鼠中的传播。 具体目标2：确定中和活性和SAG1地形 犬新城疫免疫血清中免疫球蛋白的表位特异性 等时传输。 具体目标3：确定血清抗体对中和是否敏感 表位与预防犬新孢子虫流产相关 牛群。 这项提案的成功完成将是第一项界定 抗体在细胞内保护原生动物新孢子虫中的作用 金色的。它还将直接解决免疫保护问题 通过胎盘传播寄生虫，这可能是一种常见的机制 其他顶端复合体原生动物。该提案还将识别抗体和 表位将在保护性疫苗的开发中被证明是无价的， 这是目前所有研究中最重要的方向 犬新孢子菌。此外，该提案还研究了预防初始 滋养层细胞感染--顶端复合体的关键生物学机制 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.