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

Abstract

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.

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

Figure 1

Notable variables among ADCC assays. Beyond the monoclonal or polyclonal antibodies being assessed, ADCC assays vary in terms of the viral epitopes presented, the target cells on which they are presented, the effector cells that will respond, and the readout of the biological activity assayed. Image adapted from (7).

Figure 2

Effector function assays. Antibodies elicit the activities of a diverse array of effector cell types and mechanisms, leading to the generation of a variety of in vitro assays aimed at characterizing the activity of mAb and pAb samples, and defining further insights into basic mechanisms. Image adapted from (7).