ObjectiveTo identify antigenic regions in the envelope glycoproteins of the simian immunodeficiency virus isolate, SIVsm.MethodsThirty-eight peptides were synthesized and used in site-directed enzyme-linked immunosorbent assays with sera from experimentally infected macaques.ResultsFour antibody-binding regions were identified, corresponding to the second variable region [V2; amino acids (aa) 170–196], the region homologous to V3 in HIV-1 (aa 313–346), the carboxy terminus of gp120 (aa 514–537) and the amino terminus of the transmembrane protein (aa 608–638). Serum reactivity to the V2 region was higher in surviving monkeys than in animals with an early development of simian AIDS. The antigenicity of the peptide appears to be conformationally dependent.ConclusionsThe majority of antigenic sites identified in the envelope proteins of SIV correspond to sites identified in HIV-1 and HIV-2, which further supports the use of the simian model in vaccine development. The pattern of reactivity to the V2 region suggests that absence of antibodies directed to this site might correlate with disease progression.