Subtleties and Dynamics of Antibody Function: Lessons from Bovine Antibody Fragments

The global market for antibody-based drugs is expected to double within a decade given their clinical success against diseases where conventional therapies fail. Our studies of antibody structure and function have revealed subtle differences in the role of VH and VL domains in antigen recognition and virus neutralization functions. Studies of bovine antibody fragments, such as, scFv (single chain fragment variable) highlight how a single substitution mutation in the framework-3 may influence viral neutralization potency. The viral neutralization potency of bivalent diabody, i.e., dimerized scFv, is almost doubly enhanced when compared to its monomeric form as scFv. Further scFv multimerization as triand tetrabody does not necessarily enhance virus neutralization function. Future design of antibody-based drugs should take into consideration subtle structural modifications in the framework regions that may influence the desired function.