Antibodies and Congenital Neospora Caninum Transmission

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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.