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

Annacarmen Petrizzo,Franco M Buonaguro,Maria Tagliamonte,Maria Lina Tornesello,Luigi Buonaguro

doi:10.1186/1479-5876-12-11

Abstract

BackgroundWe 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.MethodPeripheral 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.ResultsThe 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.ConclusionThe 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.

Highlights

Hepatitis C virus (HCV) is a Hepacivirus of the Flaviviridae family, mainly involved in hepatic disorders, including chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) [1].HCV has been recognized as the major etiologic factor of type II mixed cryoglobulinemia (MC), an autoimmune disease leading to B cell non-Hodgkin’s lymphoma (NHL) in about 10% of MC patients [2,3,4,5].The clonal B cell expansion is characterized by the production of an Ig molecule expressing a unique combination of antigen-specific sequences, the so called idiotype (Id)
We have previously reported the results of the effect of the IGKV3-20 candidate idiotype vaccine on ex vivo stimulated Peripheral blood mononuclear cells (PBMCs), as experimental platform for evaluation and prediction of responsiveness to vaccination [9]
Cytokine pattern induced in circulating antigen presenting cells (APCs) PBMCs obtained from enrolled subjects were incubated with IGKV3-20 for 24 h and 6 days and, at each timepoint, levels of Th1 (IL-2 and TNF-α) and Th2 (IL-5, IL6 and IL-10) cytokines were assessed by ELISA in the culture supernatant

Summary

Introduction

Hepatitis C virus (HCV) is a Hepacivirus of the Flaviviridae family, mainly involved in hepatic disorders, including chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) [1].HCV has been recognized as the major etiologic factor of type II mixed cryoglobulinemia (MC), an autoimmune disease leading to B cell non-Hodgkin’s lymphoma (NHL) in about 10% of MC patients [2,3,4,5].The clonal B cell expansion is characterized by the production of an Ig molecule expressing a unique combination of antigen-specific sequences, the so called idiotype (Id). 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. 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. 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

Methods

Results

Conclusion