Deciphering Fc-mediated Antiviral Antibody Functions in Animal Models

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

Ab concentration is a familiar variable insofar as a concentration threshold is typically observed, below which a given Ab (monoclonal or polyclonal) is apparently ineffectual. Related, however, is the role of Ab biodistribution (its concentration at the necessary site of activity) which may undermine Ab effectiveness by providing insufficient concentration in critical sites including solid tumors, brain, retina, intestine, lung, and testes (55) . Experimentally, as in animal models described here, there is a particular hazard at the opposite end of Ab concentration, i.e., the impulse to empirically screen for Ab effectiveness using high-dose treatments is contraindicated (as a singular approach) by the phenomenon of high-dose prozone, which presumably results from a diminution of the formation of complexes necessary for robust Fc-FcR interactions (56) , akin to highdose prozone in classical immunoprecipitation reactions. Another explanation offered [outside the binding-valency model (56) ] is that the encounter between high Ab dose and high Ag burden results in an exhaustion of complement components (especially C2 and C4) with the consequence of diminished overall antibody effectiveness in vivo (15) .