Mimotope vaccination--from allergy to cancer

Abstract

Background: Mimotopes are peptides mimicking protein, carbohydrates or lipid epitopes and can be generated by phage display technology. When selected by antibodies, they represent exclusively B-cell epitopes and are devoid of antigen/allergen-specific T-cell epitopes. Coupled to carriers or presented in a multiple antigenic peptide form mimotopes achieve immunogenicity and induce epitope-specific antibody responses upon vaccination.

Objective/methods: In allergy IgG antibodies may block IgE binding to allergens, whereas other IgG antibody specificities enhance this and support the anaphylactic reaction. In cancer, inhibitory antibody specificities prevent growth signals derived from overexpressed oncogenes, whereas growth-promoting specificities enhance signalling and proliferation. Therefore, the mimotope concept is applicable to both fields for epitope-specific vaccination and analysis of conformational B-cell epitopes for the allergen/antigen.

Results/conclusions: Mimotope technology is a relatively young theme in allergology and oncology. Still, proof of concept studies testing allergen and tumour mimotope vaccines suggest that mimotopes are ready for clinical trials.

Figure 1. The effects of IgG in allergy and cancer

Depending on their epitope specificity IgG antibodies can either inhibit or promote allergic reactions or tumour growth. A. In allergy, specific IgGs enhance the IgE binding to allergens and the anaphylactic reaction, which could be due to supporting the crosslinking capability of allergens. B. On the one hand, inhibitory IgG antibodies which recognize the IgE epitope on the allergen directly block the binding of IgE to the allergen, thus, preventing mediator release. On the other hand, IgGs can act via the FcγRIIb receptor: On B-cells this results in an inhibition of IgE-facilitated antigen presentation. The inhibitory effect on FcεRI positive effector cells is not illustrated. C. In cancer, heterodimerization of HER-2, HER-3 and other family members leads to signalling and proliferation. Therefore, antibodies promoting heterodimerization are detrimental. D. In contrast, IgG antibodies hindering heterodimerization prevent signal transduction and cell growth.

Figure 2. The principle of mimotopes

The first step in generating mimotopes is the choice of an antibody recognizing the allergen/antigen of interest. In allergy, biopanning can be carried out with allergen-specific IgE whereas in cancer, an inhibitory monoclonal antibody against the tumour antigen of interest is chosen. During biopanning mimotopes are selected and further investigated for specificity to the original antibody. Afterwards, mimotopes are tested for their ability to compete with the native allergen/antigen for binding to the original antibody. The selected mimotope is coupled to a carrier and used for immunization studies. After successful immunization, mice produce antibodies against the same epitope of the original allergen/antigen which is recognized by the antibody used for biopanning.