Prediction of individual immune responsiveness to a candidate vaccine by a systems vaccinology approach
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RESEARCH
Open Access
Prediction of individual immune responsiveness to a candidate vaccine by a systems vaccinology approach Annacarmen Petrizzo, Maria Tagliamonte, Maria Lina Tornesello, Franco M Buonaguro and Luigi Buonaguro*
Abstract 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. Keywords: Hepatitis C Virus, Non-Hodgkin’s Lymphoma, Idiotype vaccine, Immune response, Systems biology
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 also been recognized as the major etiologic factor of type II mixed cryoglobulinemia (MC), an autoimmune disease ultimately leading to B cell non-Hodgkin’s lymphoma (NHL) in about 10% of MC patients [2-5]. 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). Therefore, the Id can be a suitable target for
* Correspondence: [email protected] Laboratory of Molecular Biology and Viral Oncology, Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, “Fondazione Pascale” - IRCCS, Naples, Italy
active, as well as passive immune-therapeutic strategies to eliminate the B cells driving the tumor [6,7]. In this respect, the IGKV3-20 idiotype has been selected as a potential target of either passive immune therapy or active vaccine strategy [8]. We have previously reported the results of the effect of the IGKV3-20 candidate idiotype vaccine
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