Sagacious epitope selection for vaccines, and both antibody-based therapeutics and diagnostics: tips from virology and oncology

Abstract

The target of an antibody plays a significant role in the success of antibody-based therapeutics and diagnostics, and vaccine development. This importance is focused on the target binding site-epitope, where epitope selection as a part of design thinking beyond traditional antigen selection using whole cell or whole protein immunization can positively impact success. With purified recombinant protein production and peptide synthesis to display limited/selected epitopes, intrinsic factors that can affect the functioning of resulting antibodies can be more easily selected for. Many of these factors stem from the location of the epitope that can impact accessibility of the antibody to the epitope at a cellular or molecular level, direct inhibition of target antigen activity, conservation of function despite escape mutations, and even noncompetitive inhibition sites. By incorporating novel computational methods for predicting antigen changes to model-informed drug discovery and development, superior vaccines and antibody-based therapeutics or diagnostics can be easily designed to mitigate failures. With detailed examples, this review highlights the new opportunities, factors, and methods of predicting antigenic changes for consideration in sagacious epitope selection.

Keywords: antibody engineering; antibody targeting; antigen selection; drug targeting; epitope accessibility; epitope selection; model-informed drug discovery and development; protein engineering.