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Front Immunol. 2019 May 10;10:1025. doi: 10.3389/fimmu.2019.01025. eCollection 2019.

Knowns and Unknowns of Assaying Antibody-Dependent Cell-Mediated Cytotoxicity Against HIV-1.

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Division of Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, United States.
Thayer School of Engineering, Dartmouth College, Hanover, NH, United States.
Viral Evolution and Transmission Unit, Department of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
INSERM U1109, Fédération Hospitalo-Universitaire (FHU) OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institues of Health, Bethesda, MD, United States.
Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, United States.
Department of Surgery and Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, United States.
Global HIV Vaccine Enterprise, New York, NY, United States.


It is now well-accepted that Fc-mediated effector functions, including antibody-dependent cellular cytotoxicity (ADCC), can contribute to vaccine-elicited protection as well as post-infection control of HIV viremia. This picture was derived using a wide array of ADCC assays, no two of which are strictly comparable, and none of which is qualified at the clinical laboratory level. An earlier comparative study of assay protocols showed that while data from different ADCC assay formats were often correlated, they remained distinct in terms of target cells and the epitopes and antigen(s) available for recognition by antibodies, the effector cells, and the readout of cytotoxicity. This initial study warrants expanded analyses of the relationships among all current assay formats to determine where they detect overlapping activities and where they do not. Here we summarize knowns and unknowns of assaying ADCC against HIV-1.


ADCC—antibody dependent cellular cytotoxicity; Fc receptor; HIV—human immunodeficiency virus; antibodies; effector function

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