Will Systems Biology Deliver Its Promise and Contribute to the Development of New or Improved Vaccines?

Abstract

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.

Methods for predicting vaccine immunogenicity and reactogenicity

“…Most system vaccinology papers have applied transcriptomics to study the dynamics of vaccine response in PBMCs. 47 Nevertheless, variation in mRNA levels observed in blood can reflect both changes in cell frequency and in mRNA abundance. 7 Moreover, different cell populations present diverse patterns in activation of biological pathways, production of proteins or gene methylation in response to perturbations.…”

The role of systems biology approaches in determining molecular signatures for the development of more effective vaccines

“…Humans are rarely homozygous for many genes, while inbred mice are homozygous across most of their genome. Even using primates as an animal model to predict success of HIV vaccine has been unreliable [11]. While animal models have their uses, humans are the best model for truly understanding human immunity.…”

Using Omics Technologies and Systems Biology to Identify Epitope Targets for the Development of Monoclonal Antibodies Against Antibiotic-Resistant Bacteria

“…More empirical approaches may have achieved their previous successes because experimental screenings are better equipped to accommodate the degenerate and flexible nature of the immune system. Nevertheless, massive data and systemic approaches have likely not yet been successful, not because of their lack of potential, but because of the interpretation of results (51,52). In addition, there is room for improvement for rational approaches through the collection of new data, algorithms, and paradigms, and this is a continuous process, whereas screening and expert selection are probably closer to their respective plateaus.…”