Journal
CURRENT HIV RESEARCH
Volume 15, Issue 3, Pages 202-215Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1570162X15666170320112247
Keywords
HIV; antibodies; IG; Fc receptors; natural killer cells; ADCC; ADCP; vaccine
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Funding
- Australian National Health and Medical Research Council
- Victorian Operational Infrastructure Scheme
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Background: There is now intense interest in the role of HIV-specific antibodies and the engagement of Fc gamma R 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 Fc-dependent 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 Fc gamma R 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 Fc gamma R ectodomains to detect functionally relevant viral antigen-specific antibodies. Results: The binding of these dimeric Fc gamma R 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 Fc gamma R 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.
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