Deciphering Fc-mediated Antiviral Antibody Functions in Animal Models

Schmaljohn, Alan L.; Orlandi, Chiara; Lewis, George K.

Epitope topology and membrane proximity can determine spatial relationships and steric hindrances that favor one type of Fc-mediated effector function over another, illustrated for example in the development of therapeutic anti-CD20 Abs (40, 57) and strongly implied with a panel of influenza-specific MAbs (6) . Some current data suggest that: ". . . complementdependent cytotoxicity and Ab-dependent cellular cytotoxicity favored a membrane-proximal epitope, whereas Ab dependent cellular phagocytosis favored an epitope positioned further away." (57) More broadly, the favored (optimal) configuration for a given effector function may vary with different Ag-Ab pairs, exemplified by counter-examples in which HIV-specific MAbs against the "membrane proximal region" of envelope may have negligible effector function (22) . Generalizations are difficult, as they are confounded by mechanistic differences between in vitro assays (17); in vivo efficacy will be decisive.