The applicant proposes to study the role of CTL's in the control of transplacental Neospora caninum transmission in an outbred bovine host. Mammalian hosts infected with N. caninum experience recrudescence of infection and tachyzoite parasitemia during immune suppression or pregnancy leading to fetal infection, parasitic encephalitis, and persistence of infection within some host populations via vertical transmission. Cytotoxic T lymphocytes (CTL s) are important in immune control of murine infections with T. gondii, demonstrated by adoptive transfer and depletion studies. CD8+ cytotoxic effectors and a dominant type 1 immune response correlate with resolution of intracellular apicomplexan infections. Mice immunized with SAG1, an immunodominant surface protein of T. gondii develop protective immunity that can be adoptively transferred with SAG1 specific CTL's. CD8+ T lymphocytes from mice infected with N. caninum antigen protect against challenge with T. gondii, suggesting that protective CTLs may be induced by homologous antigens. In murine pregnancy models of neosporosis, neutralization of a type 2 response together with N. caninum antigen priming prior to gestation decrease transplacental transmission. The proposed research will test the hypothesis that immunization with N. caninum antigens recognized by cytotoxic lymphocytes will limit congential N. caninum transmission in cattle. The project focuses upon NcSAG1, the major surface antigen.
|Staska, Lauren M; Davies, Christopher J; Brown, Wendy C et al. (2005) Identification of vaccine candidate peptides in the NcSRS2 surface protein of Neospora caninum by using CD4+ cytotoxic T lymphocytes and gamma interferon-secreting T lymphocytes of infected holstein cattle. Infect Immun 73:1321-9|
|Staska, Lauren M; McGuire, Travis C; Davies, Christopher J et al. (2003) Neospora caninum-infected cattle develop parasite-specific CD4+ cytotoxic T lymphocytes. Infect Immun 71:3272-9|