Deciphering Fc-mediated Antiviral Antibody Functions in Animal Models

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

The network of interactions between virus and host is not only complicated, it represents a complex adaptive system of which Ab-mediated immunity is only one important part. Despite the bewildering complexity, some useful generalizations have emerged: in vivo veritas; or in a colloquial tautology used in reference to viral vaccines and therapies, the only correlate of protection is protection. Direct testing of effectiveness in human trials is the ideal benchmark for licensure of vaccines and therapies for human use; however, in cases for which human testing is unfeasible or unethical (1, 2) , indirect rationales for product licensure must be established on the basis of animal models. That is, where human health is the predominant ultimate concern of research and development, and is the standard benchmark of its relevance, the most meaningful in vitro assays along with non-human models of disease are sometimes necessary surrogates for human efficacy trials. And while in vitro assays can be highly useful as possible statistical correlates of protection (3) , they can also be poor reflections of complex realities: witness the abundant examples in which neutralization, binding titer, or hemagglutinationinhibition assays can be inadequate at best, misleading at worst (4) (5) (6) . The fullness of what we wish to know about antiviral Abs is to be found in how Abs limit or sometimes exacerbate virus-precipitated disease in the body of an animal.