VOLUME 3 NUMBER 2 (July to December 2010)

A method for designing molecules for use in directing the antibody response to a chosen region of a protein antigen

A purely computational method is proposed for reducing the antigenicity of a protein molecule, except that of a chosen region, so that the modified molecule, when used as an immunogen, would be expected to elicit an antibody response that is primarily directed at the chosen region. The chosen region could be a site that is critical to the structure or biological activity of the molecule, for example, a binding site for specific ligand, a catalytic site, a region that undergoes structural change for effective function, a neutralizing antibody epitope, etc. The method consists of (1) identifying the antibody epitopes that include the chosen region or part of it and (2) by judicious replacement of the amino acid residues, reducing the antigenicity of all the antibody epitopes of the molecule, except for those which include the chosen region. The method is useful in the design of vaccines, or of immunogens for the production of antibodies for various biochemical and medical applications. The method can also be used to design a molecule whose antigenicity is generally suppressed while preserving a critical region, e.g., when "humanizing" a nonhuman antibody by reducing the antigenicity of the framework regions while preserving the structure and properties of the antigen-binding region.