Will Systems Biology Deliver Its Promise and Contribute to the Development of New or Improved Vaccines? Seeing the Forest Rather than a Few Trees

: Preventing morbidity and mortality from infectious disease through the development and use of effective vaccines is one of medicine's greatest achievements and greatest frustrations. We are struggling with improving vaccine efficacy for some of the most globally widespread diseases, such as malaria and tuberculosis. In an effort to gain an edge, systems biology approaches have begun to be employed to more broadly investigate the pathways leading to protective vaccine responses. As such, we are now at a critical juncture, needing to evaluate how fruitful these approaches have been. Herein we discuss the level of success achieved as compared to the original promise of systems methodologies, and conclude that while we have indeed begun to make clear inroads into understanding the immune response to vaccines, we still have much to learn and gain from the more comprehensive approach of systems-level analysis.