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    Antibody Functional Assays as Measures of Fc Receptor-Mediated Immunity to HIV - New Technologies and their Impact on the HIV Vaccine Field

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    Author
    Wines, BD; Billings, H; Mclean, MR; Kent, SJ; Hogarth, PM
    Date
    2017-01-01
    Source Title
    Current HIV Research
    Publisher
    BENTHAM SCIENCE PUBL LTD
    University of Melbourne Author/s
    Wines, Bruce; Kent, Stephen; McLean, Milla; Hogarth, Phillip
    Affiliation
    Microbiology and Immunology
    Clinical Pathology
    Metadata
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    Document Type
    Journal Article
    Citations
    Wines, B. D., Billings, H., Mclean, M. R., Kent, S. J. & Hogarth, P. M. (2017). Antibody Functional Assays as Measures of Fc Receptor-Mediated Immunity to HIV - New Technologies and their Impact on the HIV Vaccine Field. CURRENT HIV RESEARCH, 15 (3), pp.202-215. https://doi.org/10.2174/1570162X15666170320112247.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/258384
    DOI
    10.2174/1570162X15666170320112247
    Abstract
    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.

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