Immunization with phage-displayed mimotopes

Phage-displayed mimotopes (phagotopes) are selected from random peptide libraries, because they bind to specific antibodies, thus behaving as antigenic mimics that resemble to some extent the original antigen. If the positive image of the antigen (Ag) these mimotopes provide is accurate enough to induce the production of specific antibodies (Ab) in animals, the mimotopes prove to be suitable substitute immunogens, totally distinct from the original antigen (that raised the antibodies used to identify the phagotopes). At present, the only feasible way of assessing this capability is the active immunization of experimental animals. Filamentous phages are known to be excellent immunogens; de la Cruz and collaborators first proposed using filamentous phage as immunological carriers, by cloning short peptides derived from the malaria circumsporozoite at the N terminus of pIII. Greenwood et al. cloned malaria peptides at the N terminus of the major coat protein VIII and Minenkova et al. cloned an antigenic determinant of human immunodeficiency virus (HIV) gag protein fused to pVIII and used the recombinant phage to successfully immunize rabbits. Similarly, when Willis et al. immunized mice with malaria peptides fused to pVIII, they not only obtained an antibody response, but also demonstrated that the response in mice is T-cell dependent and undergoes class switching from immunoglobulin M (IgM) to IgG. Mimotopes, selected by using either hepatitis B virus surface antigen (HBsAg)-specific monoclonal antibodies or human sera, have been used to induce HBsAg-specific antibodies in both mice and rabbits.