Technical Abstract: This study evaluated the efficacy of prime-boost vaccination for immune control of caprine arthritis-encephalitis virus (CAEV), a macrophage tropic lentivirus that causes progressive arthritis in the natural host. Vaccination of Saanen goats with pUC-based plasmid DNA expressing CAEV env induces T helper type I (Thl) biased immune responses to vector-encoded surface envelope (SU), and the plasmid-primed Thl response is expanded following boost with purified SU in Freund's incomplete adjuvant (SU-FIA) (I. C. Beyer et al., 2001, Vaccine 19, 1643-1651). Four goats vaccinated with env expression plasmids and boosted with SU-FIA were challenged intravenously with 1 X 104 TCID 50 of CAEV at 428 days after SU-FIA boost and evaluated by immunological, virological, and disease criteria. Controls included two goats primed with pUCI8 and eight unvaccinated goats. Goats receiving prime-boost vaccination with CAEV env plasmids and SU-FIA became infected but suppressed postchallenge virus replication, provirus loads in lymph node, and development of arthritis for at least 84 weeks.