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      Tonsil explants as a human in vitro model to study vaccine responses

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          Abstract

          Introduction

          Vaccination is one of the most effective infection prevention strategies. Viruses with high mutation rates -such as influenza- escape vaccine-induced immunity and represent significant challenges to vaccine design. Influenza vaccine strain selection is based on circulating strains and immunogenicity testing in animal models with limited predictive outcomes for vaccine effectiveness in humans.

          Methods

          We developed a human in vitro vaccination model using human tonsil tissue explants cultured in 3D perfusion bioreactors to be utilized as a platform to test and improve vaccines.

          Results

          Tonsils cultured in bioreactors showed higher viability, metabolic activity, and more robust immune responses than those in static cultures. The in vitro vaccination system responded to various premanufactured vaccines, protein antigens, and antigen combinations. In particular, a multivalent in vitro immunization with three phylogenetically distant H3N2 influenza strains showed evidence for broader B cell activation and induced higher antibody cross-reactivity than combinations with more related strains. Moreover, we demonstrate the capacity of our in vitro model to generate de novo humoral immune responses to a model antigen.

          Discussion

          Perfusion-cultured tonsil tissue may be a valuable human in vitro model for immunology research with potential application in vaccine candidate selection.

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          Most cited references49

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          QuPath: Open source software for digital pathology image analysis

          QuPath is new bioimage analysis software designed to meet the growing need for a user-friendly, extensible, open-source solution for digital pathology and whole slide image analysis. In addition to offering a comprehensive panel of tumor identification and high-throughput biomarker evaluation tools, QuPath provides researchers with powerful batch-processing and scripting functionality, and an extensible platform with which to develop and share new algorithms to analyze complex tissue images. Furthermore, QuPath’s flexible design makes it suitable for a wide range of additional image analysis applications across biomedical research.
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            Nextstrain: real-time tracking of pathogen evolution

            Abstract Summary Understanding the spread and evolution of pathogens is important for effective public health measures and surveillance. Nextstrain consists of a database of viral genomes, a bioinformatics pipeline for phylodynamics analysis, and an interactive visualization platform. Together these present a real-time view into the evolution and spread of a range of viral pathogens of high public health importance. The visualization integrates sequence data with other data types such as geographic information, serology, or host species. Nextstrain compiles our current understanding into a single accessible location, open to health professionals, epidemiologists, virologists and the public alike. Availability and implementation All code (predominantly JavaScript and Python) is freely available from github.com/nextstrain and the web-application is available at nextstrain.org.
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              Of Mice and Not Men: Differences between Mouse and Human Immunology

              Mice are the experimental tool of choice for the majority of immunologists and the study of their immune responses has yielded tremendous insight into the workings of the human immune system. However, as 65 million years of evolution might suggest, there are significant differences. Here we outline known discrepancies in both innate and adaptive immunity, including: balance of leukocyte subsets, defensins, Toll receptors, inducible NO synthase, the NK inhibitory receptor families Ly49 and KIR, FcR, Ig subsets, the B cell (BLNK, Btk, and lambda5) and T cell (ZAP70 and common gamma-chain) signaling pathway components, Thy-1, gammadelta T cells, cytokines and cytokine receptors, Th1/Th2 differentiation, costimulatory molecule expression and function, Ag-presenting function of endothelial cells, and chemokine and chemokine receptor expression. We also provide examples, such as multiple sclerosis and delayed-type hypersensitivity, where complex multicomponent processes differ. Such differences should be taken into account when using mice as preclinical models of human disease.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/2731560Role: Role: Role: Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/540804Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/205453Role: Role: Role:
                Role: Role: Role:
                Role: Role: Role: Role:
                Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/62307Role: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role:
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                17 September 2024
                2024
                : 15
                : 1425455
                Affiliations
                [1] 1 Translational Immunology, Department of Biomedicine, University of Basel , Basel, Switzerland
                [2] 2 Tissue Engineering, Department of Biomedicine, University of Basel and University Hospital Basel , Basel, Switzerland
                [3] 3 Ear Nose Throat Clinic, University Hospital Basel , Basel, Switzerland
                [4] 4 Institute of Medical Genetics and Pathology, University Hospital Basel , Basel, Switzerland
                [5] 5 Department of Biomedical Engineering, University of Basel , Allschwil, Switzerland
                [6] 6 University Center of Immunology, University Hospital Basel , Basel, Switzerland
                Author notes

                Edited by: Rajko Reljic, University of London, United Kingdom

                Reviewed by: Alastair Copland, University of Birmingham, United Kingdom

                Jasper J Koning, Amsterdam University Medical Cen, Netherlands

                *Correspondence: Christoph T. Berger, christoph.berger@ 123456usb.ch
                Article
                10.3389/fimmu.2024.1425455
                11442277
                39355250
                19d44b8c-a275-4e8e-ba8f-17a9cf64da43
                Copyright © 2024 Bonaiti, Muraro, Robert, Jakscha, Dirnhofer, Martin and Berger

                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
                : 29 April 2024
                : 28 August 2024
                Page count
                Figures: 6, Tables: 0, Equations: 0, References: 50, Pages: 14, Words: 7508
                Funding
                Funded by: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung , doi 10.13039/501100001711;
                Award ID: 310030_192440
                Funded by: Uniscientia Foundation , doi 10.13039/501100017659;
                Award ID: n/a
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The study was funded by the Uniscientia Foundation and supported by the SNSF (310030_192440) (both to CB).
                Categories
                Immunology
                Original Research
                Custom metadata
                Vaccines and Molecular Therapeutics

                Immunology
                tonsil,bioreactor, in vitro model,vaccines,influenza,antibodies,human
                Immunology
                tonsil, bioreactor, in vitro model, vaccines, influenza, antibodies, human

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