EPITOPE DISCOVERY--A NEW ROUTE TO VACCINES

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Bacteriophage T4 serves as a model ~pathogen~ for evaluation a new vaccine development strategy called epitope discovery. The goal is to find artificial mimics of authentic pathogen B-epitopes that can serve as components of an effective vaccine. The source of mimics are large libraries of random peptides genetically fused to the surface of filamentous phage-display vectors. Mouse anti-pathogen antibodies--we call them direct antibodies because they are elicted directly by the pathogen--have been used to affinity select clones out of the phage libraries whose displayed peptides bind them strongly. These peptides are antigenic mimics of the corresponding authentic pathogen epitopes. Are they also immunogenic mimics, in the sense that they elicit an antibody response that cross-reacts with the pathogen itself? That is a vital question in evaluating the promise of epitope discovery for vaccine development, since only immunogenic mimics can have disease-protective value. Accordingly, a panel of antigenic mimics will be assessed for two key components of immunogenic mimicry. First, mice will be hypperimmunized with each of the antigenic mimics and the resulting indirect antibodies titered against both the antigenic mimic and the authentic pathogen epitope. Comparable titers would indicate that the former is a good immunogenic mimic of the latter. Second, mice will be primed with antigenic mimics (long with appropriate T epitopes) to determine if the resulting memory B cells can be mobilized by a challenge with the pathogen itself.