The role of sustained antibody-dependent cell-mediated cytotoxicity (ADCC) in SIV-infected macaques in the delayed progression to AIDS

An effective AIDS vaccine must elicit all protective host immune responses. Although several in vitro lines of evidence support the potential power of antibody-dependent cell-mediated cytotoxicity in controlling HIV infection, the role of ADCC in the pathogenesis of HIV infection in vivo remains uncertain. There are few studies to date that simultaneously and longitudinally determine the plasma ADCC activity and NK cell activity in HIV-infected subjects. Without determining the competence of the effector cell for ADCC, measuring plasma ADCC activity alone will not firmly establish the existence of ADCC in vivo. Further, the reason for differences in ADCC plasma activity between non-AIDS and AIDS plasma in cases where there are similar antibody titers warrants exploration as the cause may shed light on therapeutic interventions. Finally, there are no studies that determine the effect of the controlled abrogation of ADCC on HIV disease progression. The nonhuman primate model for HIV/AIDS is the best system for such studies. The specific aims of the work presented here are (1) to measure plasma ADCC activity among SIV-infected macaques longitudinally and to determine its relationship to the rate of disease progression; (2) to longitudinally determine the fraction of total IgG that is ADCC-mediating in SIV-infected macaque plasmas; and (3) to develop reagents that can be used to determine the effect of in vivo CD 16 blockade on direct ADCC activity of SIV-infected macaque PBMC and progression to AIDS. Such longitudinal and in vivo studies are required to firmly establish a protective role of ADCC in the progression to AIDS and to determine the potential importance of eliciting ADCC-mediating antibodies in a potential vaccine against HIV.