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.