|Dyer, Robert - U DELAWARE, NEWARK|
Submitted to: BARC Poster Day
Publication Type: Abstract Only
Publication Acceptance Date: April 2, 2003
Publication Date: April 15, 2003
Citation: Tuo, W., Dubey, J.P., Gasbarre, L.C., Jenkins, M.C., Zarlenga, D.S., Fetterer, R.H., Dyer, R., Boyd, P., Paape, M.J. 2003. Immunological and molecular strategies to control neosporosis in cattle. BARC Poster Day. Technical Abstract: Neospora caninum is an apicomplexan parasite that infects a number of cell types, causing neosporosis in several species including cattle. In the past decade, neosporosis has been recognized as a primary cause of abortion in cattle worldwide. It was estimated that approximately 20% of all bovine abortions are attributed to neosporosis; Neospora-related abortion costs the cattle industry 35-40 million dollars a year in the state of California alone. In infected cows, N. caninum elicits a strong humoral immune response as indicated by high circulating antibody titers, whereas N. caninum-induced cell-mediated immune response is poorly understood. Previous exposure to, or infection by, the parasite does not provide protection against abortion, in spite of the presence of Neospora specific antibodies. Our current hypothesis is that the host immunity may be influenced by potent nonspecific antigens (superantigens) of N. caninum upon infection or immunization, leading to T cell unresponsiveness in subsequent infection. Intracellular parasites such as N. caninum require an antigen-specific T helper (Th) 1 immune response (represented by high levels of T cell proliferation and type 1 cytokine production) for host protection. Our focus is to understand the N. caninum-host interaction and the knowledge gained from this research will be used to develop a vaccine that can stimulate antigen-specific cell-mediated immune response against N. caninum and confer protection upon exposure in cattle. Parasite antigens are being screened for immunodominance by antigen-specific T cell proliferation and cytokine production (RT-PCR, bioassay and ELISA). Regulatory molecules affecting parasite replication and/or survival are being determined using a parasite survival assay and RNA interference technology. Genes encoding the immunodominant antigens will be cloned, sequenced and engineered for the production of recombinant proteins which will be used in a multivalent vaccine for neosporosis. Preliminary results from 28 cows showed that whole parasite antigen preparation of N. caninum contained a component(s) that had potent non-specific lymphocyte stimulatory activity. This effect was not likely due to bacterial endotoxin contamination. The nature of this component and its effect on cytokine production are under investigation in this lab. It is speculated that the presence of nonspecific stimulatory factors in N. caninum may compromise the development of a parasite specific immune response during infection. Further understanding of the interaction between the parasite and host will facilitate the development of an effective vaccine for bovine neosporosis.