Antibody response to the surface envelope of caprine arthritis-encephalitis lentivirus: disease status is predicted by SU antibody isotype.

This study evaluated the hypothesis that the disease status of Saanen goats infected with caprine arthritis-encephalitis lentivirus (CAEV) is associated with the focus of immune responses to viral antigens, particularly the surface envelope glycoprotein (SU). Specifically, we have proposed that Th2 responses promote progressive immune-mediated arthritis, whereas Th1 responses restrict virus replication and development of clinical disease. The present study determined the isotype of SU antibodies associated with progressor and long-term nonprogressor (LTNP) status. We show that chronically infected goats that develop clinical arthritis have predominantly IgG1 antibodies to SU during both preclinical and clinical stages of disease, whereas SU antibodies of LTNP goats are relatively biased toward IgG2. Additional studies determined the isotype of SU antibodies induced initially by CAEV infection. These experiments show that initial IgG1-dominated responses to SU are associated with subsequent development of preclinical inflammatory joint lesions, whereas lack of joint pathology is associated with an IgG2 bias of initial responses to SU. Our results using the CAEV model suggest that isotype bias of SU antibodies is a reliable indicator of clinical disease caused by lentiviruses. Isotype analysis may be a useful method to screen candidate lentiviral vaccines intended to prevent disease progression.