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

While whole killed, whole protein, or live attenuated vaccines were the standard bearers for protective vaccines in the last century, there are concerns about their safety. New vaccine design techniques are contributing to an emphasis on vaccines developed using the minimum essential subset of T- and B-cell epitopes that comprise the “immunome.” We have used bioinformatics sequence analysis tools, epitope-mapping tools, microarrays and high-throughput immunology assays to identify the minimal essential vaccine components 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) mouse models and the p27 knockout mouse (for H. pylori). Such immunome-derived vaccines have 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 vaccine protection 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 vaccines is discussed.