Immunome-derived Epitope-driven Vaccines (ID-EDV) Protect against Viral or Bacterial Challenge in Humanized Mice

Abstract While whole killed, whole protein, or live attenuated vaccineswere the standard bearers for protective vaccinesin the last century, there are concerns about their safety. New vaccinedesign techniques are contributing to an emphasis on vaccinesdeveloped using the minimum essential subset of T- and B-cell epitopes that comprise the “ immunome.” We have used bioinformatics sequence analysis tools, epitope-mappingtools, microarrays and high-throughput immunology assays to identify the minimal essential vaccinecomponents for smallpox, tularemia, Helicobacter pylori and tuberculosis vaccines. As will be described in this review, this approach has resulted in the development of four immunome-derived epitope-driven vaccines(ID-EDV); three of these proved protective against viral or bacterial challenge. Protective efficacies of 100% ( vaccinia), 90% (H. pylori), and 57% ( tularemia) were achieved in HLA-transgenic ( humanized) mousemodels and the p27 knockout mouse(for H. pylori). Such immunome-derived vaccineshave a significant advantage over conventional vaccines; the careful selection of the components should diminish undesired side effects such as those observed with whole pathogen and protein subunit vaccines. Here we summarize data showing prototype ID-ED vaccineprotection against lethal challenge with vaccinia, tularemia, and H. pylori in a model of infection. The tools that made these successes possible are described and the anticipated clinical development of ID-ED vaccinesis discussed.