Bivalent binding model and effect of dissociation rate on neutralization in bivalent and monovalent binding.

<p>(A) Schematic of the step-wise bivalent binding model of an IgG to two envelope spikes (Ag, antigen) tethered to the same surface (<i>k_on</i>, association rate constant; <i>k_off</i>, dissociation rate constant; <i>k_on*</i>, enhanced association rate constant resulting from the small reaction volume of Reaction 2). (B) Comparison of the effect of the Fab dissociation rate constant (<i>k_off</i>) on the neutralization potency of Fab (left) and IgG (right) variants of palivizumab, a monoclonal antibody against RSV. Adapted from Table 1 in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000908#ppat.1000908-Wu1" target="_blank">[32]</a>. The names of the Fab/IgG pairs were changed to A–G for clarity. A, AFFFd; B, AFFYd; C, AFSFd; D, AFFGd; E, W100F; F, S32A; G, wild type (see <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000908#ppat.1000908-Wu1" target="_blank">[32]</a> for an explanation of mutant nomenclature). Note that these results suggest that high affinity Fabs with slow dissociation rates (e.g., Fabs selected by techniques such as phage display) may not exhibit increased neutralization potencies, particularly against a densely packed virus, when converted to bivalent IgGs.