Background: 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 analyses of the RV144
vaccine trial, natural progression cohorts, and macaque models all point to a role for Fc-dependent effector
functions, such as cytotoxicity (ADCC) or phagocytosis (ADCP), in the control of HIV. However,
reliable assays that can be reproducibly used across different laboratories to measure Fcdependent
functions, such as antibody dependent cellular cytotoxicity (ADCC) are limited.
Method: This brief review highlights the importance of Fc properties for immunity to HIV, particularly
via FcγR diversity and function. We discuss assays used to study FcR mediated functions of
HIV-specific Ab, including our recently developed novel cell-free ELISA using homo-dimeric FcγR
ectodomains to detect functionally relevant viral antigen-specific antibodies.
Results: The binding of these dimeric FcγR ectodomains, to closely spaced pairs of IgG Fc, mimics
the engagement and cross-linking of Fc receptors by IgG opsonized virions or infected cells as the
essential prerequisite to the induction of Ab-dependent effector functions. The dimeric FcγR ELISA
reliably correlates with ADCC in patient responses to influenza. The assay is amenable to high
throughput and could be standardized across laboratories.
Conclusion: We propose the assay has broader implications for the evaluation of the quality of antibody
responses in viral infections and for the rapid evaluation of responses in vaccine development
campaigns for HIV and other viral infections.