Systems vaccinology: probing humanity's diverse immune systems with vaccines

Abstract

Homo sapiens are genetically diverse, but dramatic demographic and socioeconomic changes during the past century have created further diversification with respect to age, nutritional status, and the incidence of associated chronic inflammatory disorders and chronic infections. These shifting demographics pose new challenges for vaccination, as emerging evidence suggests that age, the metabolic state, and chronic infections can exert major influences on the immune system. Thus, a key public health challenge is learning how to reprogram suboptimal immune systems to induce effective vaccine immunity. Recent advances have applied systems biological analysis to define molecular signatures induced early after vaccination that correlate with and predict the later adaptive immune responses in humans. Such "systems vaccinology" approaches offer an integrated picture of the molecular networks driving vaccine immunity, and are beginning to yield novel insights about the immune system. Here we discuss the promise of systems vaccinology in probing humanity's diverse immune systems, and in delineating the impact of genes, the environment, and the microbiome on protective immunity induced by vaccination. Such insights will be critical in reengineering suboptimal immune systems in immunocompromised populations.

Fig. 1.

Systems vaccinology approaches to probe humanity’s immune systems. Genes, the environment, and the microbiome are three interdependent determinants of human physiology. Variations in each of these three determinants impact fundamental aspects of physiology, such as aging, nutritional status, and susceptibility to chronic infections and autoimmunities and allergies, and result in a staggering diversity of human physiologies. Recent studies have applied systems biological approaches to understand the molecular networks driving immune responses in humans. Such systems vaccinology approaches will be of great value in probing humanity’s diverse immune systems, and in enabling the rational design of vaccines that can induce effective immunity in special immunocompromised populations.

Fig. 2.

The application of systems vaccinology in clinical trials. Systems vaccinology approaches hold promise for predicting vaccine efficacy in clinical trials. (Upper Right) For vaccines with a known correlate of protection, systems approaches could be used to identify signatures induced 1 d or 3 after vaccination that is capable of predicting the later immunogenicity. Such signatures can be used to rapidly identify nonresponders in special populations. (Left) For vaccines for which challenge with the pathogen is feasible, systems approaches permit a direct identification of the correlates of protection. (Lower Right) For vaccines for which correlates are unknown, systems approaches can be applied to a retrospective nested case control study to identify novel correlates.