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      Sm-p80-based schistosomiasis vaccine mediated epistatic interactions identified potential immune signatures for vaccine efficacy in mice and baboons

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          Abstract

          Schistosomiasis is a neglected parasitic disease of major public health concern as it affects over 250 million people in developing countries. Currently there is no licensed vaccine available against schistosomiasis. The Schistosoma mansoni calpain protein, Sm-p80, is a leading vaccine candidate now ready to move to clinical trials. In order to better assess Sm-p80 vaccine immunogenicity; here we used a systems biology approach employing RNA-sequencing to identify gene signatures and epistatic interactions following Sm-p80 vaccination in mouse and baboon models that may predict vaccine efficacy. Recombinant Sm-p80 + CpG-oligodeoxynucleotide (ODN) vaccine formulation induced both cellular and humoral immunity genes with a predominant TH1 response as well as TH2 and TH17 gene signatures. Early gene responses and gene-network interactions in mice immunized with rSm-p80 + ODN appear to be initiated through TLR4 signaling. CSF genes, S100A alarmin genes and TNFRSF genes appear to be a signature of vaccine immunogenicity/efficacy as identified by their participation in gene network interactions in both mice and baboons. These gene families may provide a basis for predicting desirable outcomes for vaccines against schistosomiasis leading to a better understanding of the immune system response to vaccination.

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          Most cited references21

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          Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans.

          A major challenge in vaccinology is to prospectively determine vaccine efficacy. Here we have used a systems biology approach to identify early gene 'signatures' that predicted immune responses in humans vaccinated with yellow fever vaccine YF-17D. Vaccination induced genes that regulate virus innate sensing and type I interferon production. Computational analyses identified a gene signature, including complement protein C1qB and eukaryotic translation initiation factor 2 alpha kinase 4-an orchestrator of the integrated stress response-that correlated with and predicted YF-17D CD8(+) T cell responses with up to 90% accuracy in an independent, blinded trial. A distinct signature, including B cell growth factor TNFRS17, predicted the neutralizing antibody response with up to 100% accuracy. These data highlight the utility of systems biology approaches in predicting vaccine efficacy.
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            Systems Biology of Seasonal Influenza Vaccination in Humans

            We used a systems biological approach to study innate and adaptive responses to influenza vaccination in humans, during 3 consecutive influenza seasons. Healthy adults were vaccinated with inactivated (TIV) or live attenuated (LAIV) influenza vaccines. TIV induced greater antibody titers and enhanced numbers of plasmablasts than LAIV. In TIV vaccinees, early molecular signatures correlated with, and accurately predicted, later antibody titers in two independent trials. Interestingly, the expression of Calcium/calmodulin-dependent kinase IV (CamkIV) at day 3 was inversely correlated with later antibody titers. Vaccination of CamkIV −/− mice with TIV induced enhanced antigen-specific antibody titers, demonstrating an unappreciated role for CaMKIV in the regulation of antibody responses. Thus systems approaches can predict immunogenicity, and reveal new mechanistic insights about vaccines.
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              • Article: not found

              IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4+ T cells.

              An efficient Th1-driven adaptive immune response requires activation of the T cell receptor and secretion of the T cell stimulatory cytokine IL-12 by activated antigen-presenting cells. IL-12 triggers Th1 polarization of naive CD4(+) T cells and secretion of IFN-gamma. We describe a new heterodimeric cytokine termed IL-27 that consists of EBI3, an IL-12p40-related protein, and p28, a newly discovered IL-12p35-related polypeptide. IL-27 is an early product of activated antigen-presenting cells and drives rapid clonal expansion of naive but not memory CD4(+) T cells. It also strongly synergizes with IL-12 to trigger IFN-gamma production of naive CD4(+) T cells. IL-27 mediates its biologic effects through the orphan cytokine receptor WSX-1/TCCR.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                13 February 2017
                2017
                : 12
                : 2
                : e0171677
                Affiliations
                [1 ]Center for Tropical Medicine and Infectious Diseases, Texas Tech University School of Medicine, Lubbock, Texas, United States of America
                [2 ]Center for Tropical Medicine and Infectious Diseases, Texas Tech University School of Medicine, Amarillo, Texas, United States of America
                [3 ]Center for Biotechnology and Genomics. Texas Tech University, Lubbock, Texas, United States of America
                [4 ]Department of Internal Medicine. Texas Tech University School of Medicine, Lubbock Texas, United States of America
                [5 ]PAI Life Sciences, Seattle, Washington, United States of America
                [6 ]Infectious Disease Research Institute, Seattle, Washington, United States of America
                [7 ]Department of Global Health, University of Washington, Seattle, Washington, United States of America
                University of Illinois, UNITED STATES
                Author notes

                Competing Interests: All authors report no conflicts of interest. The collaboration with PAI Life Sciences in this manuscript included preparation and revision of the manuscript. This affiliation does not alter our adherence to all PLOS ONE policies on sharing data and materials.

                • Conceptualization: JUR MWM KRK AAS.

                • Data curation: JUR MWM KRK OEO JS.

                • Formal analysis: JUR MWM KRK AAS.

                • Funding acquisition: DC AAS.

                • Investigation: JUR MWM KRK OEO JS WZ AJM.

                • Methodology: JUR MWM KRK OEO JS WZ AJM DC AAS.

                • Project administration: JUR MWM AAS.

                • Resources: JUR MWM KRK OEO JS WZ AJM DC AAS.

                • Software: JUR MWM KRK OEO.

                • Supervision: DC AAS.

                • Validation: JUR MWM KRK OEO JS WZ AJM DC AAS.

                • Visualization: JUR MWM AAS.

                • Writing – original draft: JUR MWM KRK DC AAS.

                • Writing – review & editing: JUR MWM KRK OEO JS WZ AJM DC AAS.

                Article
                PONE-D-16-43804
                10.1371/journal.pone.0171677
                5305113
                28192534
                be19e657-0cd0-4e77-bcac-4f77e8cb5c19
                © 2017 Rojo et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 17 November 2016
                : 23 January 2017
                Page count
                Figures: 9, Tables: 0, Pages: 28
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;
                Award ID: R43AI103983
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;
                Award ID: R44AI103983
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000865, Bill and Melinda Gates Foundation;
                Award ID: OPP1097535
                Award Recipient :
                This work was supported by NIH grants [R43AI103983, R44AI103983]; Bill and Melinda Gates Foundation Grant [OPP1097535]; and the South Plains Foundation. The funder provided support in the form of salaries for authors [JUR, MWM, OEO, JS, WZ, AJM, DC, and AAS], but did not have any additional role in the study design, data collection, and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the “author contributions” section. The collaboration with PAI Life Sciences in this study includes data analysis and preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Immunology
                Vaccination and Immunization
                Vaccines
                Medicine and Health Sciences
                Immunology
                Vaccination and Immunization
                Vaccines
                Medicine and Health Sciences
                Public and Occupational Health
                Preventive Medicine
                Vaccination and Immunization
                Vaccines
                Biology and life sciences
                Organisms
                Animals
                Vertebrates
                Amniotes
                Mammals
                Primates
                Monkeys
                Old World monkeys
                Baboons
                Biology and Life Sciences
                Immunology
                Immune Response
                Medicine and Health Sciences
                Immunology
                Immune Response
                Biology and Life Sciences
                Organisms
                Animals
                Invertebrates
                Helminths
                Schistosoma
                Schistosoma Mansoni
                Biology and Life Sciences
                Immunology
                Vaccination and Immunization
                Medicine and Health Sciences
                Immunology
                Vaccination and Immunization
                Medicine and Health Sciences
                Public and Occupational Health
                Preventive Medicine
                Vaccination and Immunization
                Biology and Life Sciences
                Genetics
                Gene Expression
                Research and Analysis Methods
                Experimental Organism Systems
                Model Organisms
                Mouse Models
                Research and Analysis Methods
                Model Organisms
                Mouse Models
                Research and Analysis Methods
                Experimental Organism Systems
                Animal Models
                Mouse Models
                Biology and Life Sciences
                Physiology
                Immune Physiology
                Spleen
                Medicine and Health Sciences
                Physiology
                Immune Physiology
                Spleen
                Custom metadata
                Data are available from the NCBI with the accession numbers SRP079915, SRP081153, SRP081155, and SRP081154.

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                Uncategorized

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