Caprine arthritis-encephalitis virus (CAEV) is a lentivirus, related to the human immunodeficiency virus (HIV), that causes arthritis and encephalitis in goats. We propose to use CAEV as a prototype lentivirus to detail the mechanisms by which lentiviruses evade immune elimination. We intend to use the information to define the conditions under which sterile immunity can be elicited with native and/or modified viral antigens. Our hypothesis is that induction of sterile immunity will require elicitation of MHC- restricted cell mediated and humoral immunity to one or more viral proteins. To test the hypothesis, we will develop and use an in vitro/in vivo model system to: 1) detail the immune response to live and dead virus, 2) analyze the immunogenic properties of recombinant viral proteins expressed with a vaccinia vector, and 3) demonstrate that the in vitro response to viral proteins can be used to predict the response to viral proteins in vivo. The investigations will provide the information that will facilitate the design of an effective vaccine for HIV and an in vivo. The investigations will provide the information that will facilitate the design of an effective vaccine for HIV and an in vitro model to test the immunogenic properties of candidate vaccines before testing in the field.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA050141-03
Application #
3194426
Study Section
Special Emphasis Panel (SRC (56))
Project Start
1989-04-01
Project End
1994-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Washington State University
Department
Type
Schools of Veterinary Medicine
DUNS #
041485301
City
Pullman
State
WA
Country
United States
Zip Code
99164
Wilkerson, M J; Davis, W C; Cheevers, W P (1995) Peripheral blood and synovial fluid mononuclear cell phenotypes in lentivirus induced arthritis. J Rheumatol 22:8-15
Perry, L L; Wilkerson, M J; Hullinger, G A et al. (1995) Depressed CD4+ T lymphocyte proliferative response and enhanced antibody response to viral antigen in chronic lentivirus-induced arthritis. J Infect Dis 171:328-34
Wilkerson, M J; Davis, W C; Baszler, T V et al. (1995) Immunopathology of chronic lentivirus-induced arthritis. Am J Pathol 146:1433-43
Baszler, T V; Harwood, W G; Lester, K L et al. (1994) Characterization of caprine microglial cells and in vitro infection with caprine arthritis-encephalitis lentivirus. Lab Invest 70:933-43
Cheevers, W P; Knowles, D P; McGuire, T C et al. (1994) Caprine arthritis-encephalitis lentivirus (CAEV) challenge of goats immunized with recombinant vaccinia virus expressing CAEV surface and transmembrane envelope glycoproteins. Vet Immunol Immunopathol 42:237-51
Cheevers, W P; McGuire, T C; Norton, L K et al. (1993) Failure of neutralizing antibody to regulate CAE lentivirus expression in vivo. Virology 196:835-9
Davis, W C; Ellis, J A (1991) Individual antigens of goats. Vet Immunol Immunopathol 27:121-31
Larsen, R A; Monaghan, M L; Park, Y H et al. (1990) Identification and characterization of monoclonal antibodies reactive with bovine, caprine and ovine T-lymphocyte determinants by flow microfluorimetry. Vet Immunol Immunopathol 25:195-208