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Antigenic variation or “Deceptive Imprinting” is a common strategy by which many disease pathogens and cancer cells evade conventional vaccine strategies as well as host immune responses. The immune system has evolved to detect a register of molecular shapes that stimulate both cellular (helper and cytotoxic T cells) and humoral (B cells and antibodies) immune effector activities to neutralize the more common shapes shared by microbial and cellular invaders, which might disrupt the hosts’ physiology. Vaccine resistant pathogens have developed the ability to subvert these effector responses by displaying and presenting chemical shapes and sequences that have higher antigenic indexes than surrounding molecular structures to “decoy” the immune system. As a pathogen invades a host, the immune system preferentially makes a response to these decoy epitopes ignoring the rest of the pathogen’s structure.

The evolutionary success of pathogens employing immune decoying is the presentation of highly immunogenic epitopes, which can also undergo antigenic variation. This decoying effect is termed “Deceptive Imprinting” after the classic example of goslings imprinting on Konrad Lorenz. Such epitopes are often adjacent to those that are more conserved and serve more important structural and functional activities of the pathogen such as adhesion, binding, colonization, and/or virulence factors. This strategy keeps the immune system effectively misdirected from critical functional domains by establishing an antigenic hierarchy between genetically unstable decoy epitopes and other conserved surface structures of the pathogen. This phenomenon also appears to greatly reduce the polyclonal multi-epitope immune response to the pathogen effectively reducing the immune response to a more oligoclonal, single-epitope restricted fashion. Such a restricted response favors the emergence of immune escape mutants and is analogous to single antibiotic or anti-viral chemotherapy that often leads to drug resistant pathogens.

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