Affinity limits in B-cell epitope prediction for immunity mediated by antipeptide antibodies

Abstract

A major goal of B-cell epitope prediction is to support the design of peptide-based immunogens (e.g., vaccines) for eliciting antipeptide antibodies that protect against disease, but these antibodies fail to confer protection and even promote disease if they bind with low affinity. In the present work, the Immune Epitope Database (IEDB) was searched to obtain published thermodynamic and kinetic data on binding interactions of antipeptide antibodies. The data suggest that the affinity of the antibodies for their immunizing peptides appears to be limited in a manner consistent with previously proposed kinetic constraints on affinity maturation in vivo, and that cross-reaction of the antibodies with proteins tends to occur with lower affinity than the corresponding reaction of the antibodies with their immunizing peptides. These observations serve to better inform B-cell epitope prediction, particularly to avoid overestimation of affinity for both active and passive immunization; whereas active immunization is subject to limitations of affinity maturation in vivo and of the capacity to accumulate endogenous antibodies, passive immunization may transcend such limitations, possibly with the aid of artificial affinity-selection processes and of protein engineering. In addition to affinity, intrinsic protein disorder may be a useful supplementary criterion for B-cell epitope prediction where such disorder obviates thermodynamically unfavorable protein structural adjustments in the course of cross-reaction between antipep-tide antibodies and proteins.