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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AI049182-04
Application #
6733497
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Wali, Tonu M
Project Start
2001-05-01
Project End
2005-04-30
Budget Start
2004-05-01
Budget End
2005-04-30
Support Year
4
Fiscal Year
2004
Total Cost
$125,280
Indirect Cost
Name
Washington State University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
041485301
City
Pullman
State
WA
Country
United States
Zip Code
99164