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      Immune System Modulation by the Adjuvants Poly (I:C) and Montanide ISA 720

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          Abstract

          Adjuvants are essential for vaccine development, especially subunit-based vaccines such as those containing recombinant proteins. Increasing the knowledge of the immune response mechanisms generated by adjuvants should facilitate the formulation of vaccines in the future. The present work describes the immune phenotypes induced by Poly (I:C) and Montanide ISA 720 in the context of mice immunization with a recombinant protein based on the Plasmodium vivax circumsporozoite protein (PvCSP) sequence. Mice immunized with the recombinant protein plus Montanide ISA 720 showed an overall more robust humoral response, inducing antibodies with greater avidity to the antigen. A general trend for mixed Th1/Th2 inflammatory cytokine profile was increased in Montanide-adjuvanted mice, while a balanced profile was observed in Poly (I:C)-adjuvanted mice. Montanide ISA 720 induced a gene signature in B lymphocytes characteristic of heme biosynthesis, suggesting increased differentiation to Plasma Cells. On the other hand, Poly (I:C) provoked more perturbations in T cell transcriptome. These results extend the understanding of the modulation of specific immune responses induced by different classes of adjuvants, and could support the optimization of subunit-based vaccines.

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

            In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0550-8) contains supplementary material, which is available to authorized users.
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              Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

              Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation. We demonstrate how GSEA yields insights into several cancer-related data sets, including leukemia and lung cancer. Notably, where single-gene analysis finds little similarity between two independent studies of patient survival in lung cancer, GSEA reveals many biological pathways in common. The GSEA method is embodied in a freely available software package, together with an initial database of 1,325 biologically defined gene sets.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/1112002
                URI : https://loop.frontiersin.org/people/1748757
                URI : https://loop.frontiersin.org/people/1845229
                URI : https://loop.frontiersin.org/people/369666
                URI : https://loop.frontiersin.org/people/391779
                URI : https://loop.frontiersin.org/people/445324
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                29 June 2022
                2022
                : 13
                : 910022
                Affiliations
                [1] 1 Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo , São Paulo, Brazil
                [2] 2 Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo , São Paulo, Brazil
                Author notes

                Edited by: Manuel Elkin Patarroyo, Colombian Institute of Immunology Foundation, Colombia

                Reviewed by: Wathsala Wijayalath, Naval Medical Research Center, United States; Joseli Oliveira Ferreira, Oswaldo Cruz Foundation (Fiocruz), Brazil

                *Correspondence: Daniel Youssef Bargieri, danielbargieri@ 123456usp.br ; Irene S. Soares, isoares@ 123456usp.br

                †These authors have contributed equally to this work

                This article was submitted to Parasite Immunology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2022.910022
                9278660
                35844531
                3b0230cd-d1c9-49dc-aac3-44d37d2dd36c
                Copyright © 2022 Marques, de Melo, Novais, Soares, Bargieri and Gimenez

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 31 March 2022
                : 31 May 2022
                Page count
                Figures: 5, Tables: 0, Equations: 0, References: 59, Pages: 14, Words: 8096
                Funding
                Funded by: Instituto Serrapilheira , doi 10.13039/501100013275;
                Categories
                Immunology
                Original Research

                Immunology
                montanide,poly (i:c),plasmodium vivax,vaccine,immune response
                Immunology
                montanide, poly (i:c), plasmodium vivax, vaccine, immune response

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