Prediction of individual immune responsiveness to a candidate vaccine by a systems vaccinology approach

Background: We have previously shown that a candidate idiotype vaccine, based on the IGKV3-20 light chain protein, is able to induce activation of circulating antigen presenting cells (APCs) in both HCV-positive and HCV-negative subjects, with production of Th2-type cytokines. In addition, such a candidate idiotype vaccine induces an early gene expression pattern, characterized by the strong induction of an innate immune response, and a late pattern, characterized by a prevalent B cell response. Nonetheless, some HCV-positive individuals showed a complete lack of maturation of circulating APCs with low levels of cytokine production, strongly suggesting the possible identification of selective impairments in immune response in individual subjects. Method: Peripheral blood mononuclear cells (PBMCs) were stimulated ex vivo with IGKV3-20 for 24 h and 6 days. Analysis of the global gene expression profile as well as the cytokine pattern was performed for individual subjects. Results: The gene expression profile showed a strong agreement with the cytokine pattern. Indeed, the expression pattern of immune-related genes is highly predictive of the individual immunological phenotype. Conclusion: The overall results represent a proof of concept, indicating the efficacy of such an ex vivo screening platform for predicting individual's responsiveness to an antigen as well as guiding optimization of vaccine design. Larger cohort study will be needed to validate results observed in the study.