Acquired immune deficiency syndrome (AIDS) has become a worldwide epidemic, so the development of vaccines and antiviral agents effective against the causative agent, human T-lymphotropic virus type III (HTLV-III), is vital. This work would be greatly simplified if a suitable animal model could be developed. Here we report the isolation of an HTLV-III-related retrovirus, STLV-III/Delta, from rhesus macaques (Macaca mulatta) with transmissible simian AIDS (SAIDS) and from asymptomatic sooty mangabeys (Cercocebus atys). SAIDS was initially diagnosed in several macaques previously inoculated with tissue homogenates of mangabey origin. Western blot analysis of both the mangabey and macaque sera demonstrated the presence of antibody cross-reactive primarily with the HTLV-III proteins p24 and p61. In a related experiment, analysis of these same sera revealed simian antibody to STLV-III/Delta proteins similar, but not identical, to those of HTLV-III with estimated relative molecular masses (Mrs) of 16,000 (16K), 26K, 35K, 45K, 60K and 110K. Infection of the mangabey, an African primate, with an HTLV-III-related virus may provide a clue to the origin of HTLV-III in humans. The apparent difference in susceptibility to SAIDS-like disease between infected macaques and mangabeys suggests that these species may respond differently to STLV-III infection.

A vaccine against human immunodeficiency virus (HIV) would be highly effective in stopping the acquired immunodeficiency syndrome (AIDS) epidemic. A comprehensive evaluation of potential vaccine methodologies can be made by means of the simian model for AIDS, which takes advantage of the similarities in viral composition and disease potential between simian immunodeficiency virus (SIV) infection of rhesus macaques and HIV infection in humans. Immunization with a formalin-inactivated whole SIV vaccine potentiated with either alum and the Syntex adjuvant threonyl muramyl dipeptide (MDP) or MDP alone resulted in the protection of eight of nine rhesus monkeys challenged with ten animal-infectious doses of pathogenic virus. These results demonstrate that a whole virus vaccine is highly effective in inducing immune responses that can protect against lentivirus infection and AIDS-like disease.

Infection of the rhesus macaque (Macaca mulatta) with simian immunodeficiency virus (SIV) induces a disease similar to AIDS. We compared SIV-specific antibody and antigenemia with the progression of disease in monkeys experimentally infected with SIV/Delta isolates that varied in pathogenicity. Western blot, immunoprecipitation, and sandwich enzyme-linked immunosorbent assay of serial sera from macaques infected with attenuated virus revealed a persistent antibody response and no evidence of SIV antigenemia. Immunosuppressed macaques without central nervous system (CNS) infections responded similarly to initial infection, but antibody specific for gag or, less frequently, to gag and env determinants declined predictably before clinical disease. Monkeys with CNS infections, however, had little, if any, detectable antibody to either envelope or gag proteins, regardless of the duration of survival. SIV/Delta-specific antigenemia, evident only in immunodeficient monkeys, fluctuated reciprocally with antibody. Our data suggest that SIV/Delta-induced disease is dependent upon antigenemic episodes that, particularly in animals with CNS infection, appear coincident with diminished antibody.

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