In-silico analysis of the “memory anti-Naïve” effect in anti-viral cross-reactive responses

Of the examples of clonal competition for antigen among lymphocytes, the recently predicted “Memory anti-Naive” phenomenon occurs when the challenging antigen is not identical to the priming, and will be consequently bound with lower avidity by preexisting memory cells. In this study we use computer modeling and a systematic schedule of viral injections to disentangle the complex relationship between different lineages of effector T cells in the presence of viruses. We measure the antiviral efficiency of memory cells as well as their dominance over naive cells as a function of the antigenic distance between first and second infection. Our simulation show that at a critical range of antigenic distance memory cells, now unable to clear the infection, can however block the surge of naive clones thus preventing an effective immune response. This finding motivate us to propose the Memory anti-Naive phenomenon as the causative mechanism for the classic Original Antigenic Sin phenomenon described in the literature which occurs irregularly in returning pandemics, and also for the less glamorous, but certainly numerous and severe, cases of misfired vaccinations, and viral escapes.