HIV-specific ADCC - new technologies to study ADCC and importance for the HIV vaccine field

There is now intense interest in the role of HIV-specific antibodies and the engagement of FcγR functions in the control and prevention of HIV infection. The RV144 vaccine study, natural progression cohorts, and macaque studies all point to a role for antibody dependent cellular cytotoxicity (ADCC) in the control of HIV. However, reliable assays that can be reproducibly used across different laboratories to measure ADCC and other Fc-dependent functions of antibodies are limited. We recently developed a novel ELISA-based assay to detect the binding of viral antigen-specific antibodies to the ectodomains of homo-dimeric Fcγ receptors. These dimeric FcγR ectodomains bind closely spaced pairs of IgG Fc and mimic the engaging and cross-linking of pairs of Fc receptors by IgG-opsonized virions or infected cells. FcγR crosslinking triggers cell activation and functions such as ADCC or antibody dependent cellular phagocytosis (ADCP). Since the assay has an ELISA format and does not require activation or killing of cells, it is amenable to high throughput and could be standardized across laboratories. The dimeric FcγR ELISA has been used reliably in influenza-specific studies that correlate dimeric FcγR binding with ADCC and we propose the assay has utility for the field of HIV research and clinical trial analyses. This brief review highlights the importance of Fc functions for immunity to HIV and discusses advances in assays to study HIV-specific ADCC.