Deciphering Fc-mediated Antiviral Antibody Functions in Animal Models

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

In search of an animal model for viral disease, classical adaptation of virus by serial passage sometimes fails repeatedly, and the accumulating evidence on the nature of species barriers for any given virus may sometimes suggest that adaptation through mutation and selective pressure is highly improbable. At best, and through the lens of product licensure, Golding writes, "The establishment of animal models predictive of vaccine effectiveness in humans has been fraught with difficulties with low success rate to date."(1) Today, however, there are many ways to: (1) refashion genes of a human virus to become more likely to cause infection and disease in non-human species; (2) refashion genes of unrelated viral pathogens (e.g., ordinarily restricted to mouse or NHP) to express and incorporate presumptive "protective Ags" of human pathogens, in order to test mechanisms of immunity targeted against those antigens; (3) render a non-human species (especially mice) more human-like in susceptibility through engraftment of human cells, or through specific gene knock-ins (e.g., of human receptors for virus) and knock-outs (e.g., of host-range resistance factors such as interferon). A few examples and references are given in Table 1 .