Deciphering Fc-mediated Antiviral Antibody Functions in Animal Models

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

As noted previously (5) , the role of Fc-dependent Ab activities on viral clearance in vivo has too often been subordinated to an unfruitful "either-or" argument about relative importance of "neutralizing" vs. "non-neutralizing" Abs, when in fact many (but not all) neutralizing monoclonal MAbs (nMAbs) are also potent cell-targeting MAbs (CT-MAbs) see Boxes 1, 2. To separate the effects of conventional nAbs from Abs that also (or exclusively) exert protective effects on viral Ag-expressing cells, the literature on tumor immunology provides useful guides in work that is already well-described and continuously evolving. Obviously enough, many of the same experiments could be replicated-and rational improvements in antiviral Ab efficacies (and vaccines) possibly suggested-by testing the capacities of different Abs (in animal models with different FcR) to eliminate cells constitutively expressing viral membrane Ags of interest, as illustrated in Figure 3B . Indeed, such work has already begun (41, 42) .