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We are analyzing https://link.springer.com/article/10.1186/s12967-016-1111-6.

Title:
Adjuvant effects of a sequence-engineered mRNA vaccine: translational profiling demonstrates similar human and murine innate response | Journal of Translational Medicine
Description:
Background Prophylactic and therapeutic vaccines often depend upon a strong activation of the innate immune system to drive a potent adaptive immune response, often mediated by a strong adjuvant. For a number of adjuvants immunological readouts may not be consistent across species. Methods In this study, we evaluated the innate immunostimulatory potential of mRNA vaccines in both humans and mice, using a novel mRNA-based vaccine encoding influenza A hemagglutinin of the pandemic strain H1N1pdm09 as a model. This evaluation was performed using an in vitro model of human innate immunity and in vivo in mice after intradermal injection. Results Results suggest that immunostimulation from the mRNA vaccine in humans is similar to that in mice and acts through cellular RNA sensors, with genes for RLRs [ddx58 (RIG-1) and ifih1 (MDA-5)], TLRs (tlr3, tlr7, and tlr8-human only), and CLRs (clec4gp1, clec2d, cledl1) all significantly up-regulated by the mRNA vaccine. The up-regulation of TLR8 and TLR7 points to the involvement of both mDCs and pDCs in the response to the mRNA vaccine in humans. In both humans and mice activation of these pathways drove maturation and activation of immune cells as well as production of cytokines and chemokines known to attract and activate key players of the innate and adaptive immune system. Conclusion This translational approach not only allowed for identification of the basic mechanisms of self-adjuvantation from the mRNA vaccine but also for comparison of the response across species, a response that appears relatively conserved or at least convergent between the in vitro human and in vivo mouse models.
Website Age:
28 years and 1 months (reg. 1997-05-29).

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  • Science
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What CMS is link.springer.com built with?

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🌠 Phenomenal Traffic: 5M - 10M visitors per month


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How Does Link.springer.com Make Money? {💸}

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Keywords {🔍}

vaccine, mrna, cells, human, immune, mimic, tlr, article, pubmed, innate, response, cell, google, scholar, analysis, fig, activation, gene, expression, mice, cas, injection, vaccines, genes, mouse, treatment, rna, study, site, data, vitro, modules, humans, pathways, responses, dln, mimicpte, model, upregulation, skin, system, performed, transcriptional, phase, additional, dendritic, correlation, immunol, immunity, upregulated,

Topics {✒️}

cd14low/ccr7high/hla-drhigh/cd40high/cd80high/cd86high c-jun n-terminal kinases c-jun n-terminal kinase mariola fotin-mleczek & benjamin petsch pw03-031—activation-induced cell death hochberg false-discovery-rate method article download pdf rnalater-preserved ln biopsies dose-dependent maturation driven mitogen-activated protein kinase antibody cross-reactivity induced cd14low/hla-drhigh phenotype miscellaneous immune-related genes clear dose-dependent increase rnalater-preserved skin biopsies dose-dependent maturation effect retinoic acid-inducible gene genome-wide transcriptome analysis mimic® tw-pte increases immune cell activation/maturation immune-related gene subset viral single-stranded rna rnalater-preserved biopsy tissues log2-fold change relative mariola fotin-mleczek published manual technique human mimic®-pte modules dose-driven innate response larger-scale manner [47] messenger rna-based vaccines human leukocyte antigen-dr pre-clinical assessments including pro-inflammatory cytokines il-6 activate mimic®-pte cells live-dead aqua negative prr-selective agonists binding rig-i-mediated activity human mimic®-pte apcs enhanced mrna half-life sequence-engineered mrna vaccine yellow fever vaccine developing mrna-vaccine technologies pre-clinical animal studies privacy choices/manage cookies mimic® tw-pte tw-pte modules dose dependent reduction cell viability assessments false discovery rate immune cell populations

Schema {🗺️}

WebPage:
      mainEntity:
         headline:Adjuvant effects of a sequence-engineered mRNA vaccine: translational profiling demonstrates similar human and murine innate response
         description:Prophylactic and therapeutic vaccines often depend upon a strong activation of the innate immune system to drive a potent adaptive immune response, often mediated by a strong adjuvant. For a number of adjuvants immunological readouts may not be consistent across species. In this study, we evaluated the innate immunostimulatory potential of mRNA vaccines in both humans and mice, using a novel mRNA-based vaccine encoding influenza A hemagglutinin of the pandemic strain H1N1pdm09 as a model. This evaluation was performed using an in vitro model of human innate immunity and in vivo in mice after intradermal injection. Results suggest that immunostimulation from the mRNA vaccine in humans is similar to that in mice and acts through cellular RNA sensors, with genes for RLRs [ddx58 (RIG-1) and ifih1 (MDA-5)], TLRs (tlr3, tlr7, and tlr8-human only), and CLRs (clec4gp1, clec2d, cledl1) all significantly up-regulated by the mRNA vaccine. The up-regulation of TLR8 and TLR7 points to the involvement of both mDCs and pDCs in the response to the mRNA vaccine in humans. In both humans and mice activation of these pathways drove maturation and activation of immune cells as well as production of cytokines and chemokines known to attract and activate key players of the innate and adaptive immune system. This translational approach not only allowed for identification of the basic mechanisms of self-adjuvantation from the mRNA vaccine but also for comparison of the response across species, a response that appears relatively conserved or at least convergent between the in vitro human and in vivo mouse models.
         datePublished:2017-01-03T00:00:00Z
         dateModified:2017-01-03T00:00:00Z
         pageStart:1
         pageEnd:18
         license:http://creativecommons.org/publicdomain/zero/1.0/
         sameAs:https://doi.org/10.1186/s12967-016-1111-6
         keywords:
            mRNA
            Vaccine
            Innate
            In vitro
            MIMIC
            Adjuvant
            Human
            Mouse
            RLRs
            CLRs
            TLRs
            Self-adjuvantation
            Biomedicine
            general
            Medicine/Public Health
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            name:Journal of Translational Medicine
            issn:
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            type:
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               name:Darin K. Edwards
               url:http://orcid.org/0000-0001-5977-6258
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                     name:Sanofi Pasteur, VaxDesign Campus
                     address:
                        name:Sanofi Pasteur, VaxDesign Campus, Orlando, USA
                        type:PostalAddress
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                     address:
                        name:CureVac AG, Tübingen, Germany
                        type:PostalAddress
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               name:Heesik Yoon
               affiliation:
                     name:Sanofi Pasteur, VaxDesign Campus
                     address:
                        name:Sanofi Pasteur, VaxDesign Campus, Orlando, USA
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Nigel Horscroft
               affiliation:
                     name:CureVac AG
                     address:
                        name:CureVac AG, Tübingen, Germany
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Brian Schanen
               affiliation:
                     name:Sanofi Pasteur, VaxDesign Campus
                     address:
                        name:Sanofi Pasteur, VaxDesign Campus, Orlando, USA
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Tanya Geter
               affiliation:
                     name:Sanofi Pasteur, VaxDesign Campus
                     address:
                        name:Sanofi Pasteur, VaxDesign Campus, Orlando, USA
                        type:PostalAddress
                     type:Organization
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               name:Mariola Fotin-Mleczek
               affiliation:
                     name:CureVac AG
                     address:
                        name:CureVac AG, Tübingen, Germany
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Benjamin Petsch
               affiliation:
                     name:CureVac AG
                     address:
                        name:CureVac AG, Tübingen, Germany
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Vaughan Wittman
               affiliation:
                     name:Sanofi Pasteur, VaxDesign Campus
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ScholarlyArticle:
      headline:Adjuvant effects of a sequence-engineered mRNA vaccine: translational profiling demonstrates similar human and murine innate response
      description:Prophylactic and therapeutic vaccines often depend upon a strong activation of the innate immune system to drive a potent adaptive immune response, often mediated by a strong adjuvant. For a number of adjuvants immunological readouts may not be consistent across species. In this study, we evaluated the innate immunostimulatory potential of mRNA vaccines in both humans and mice, using a novel mRNA-based vaccine encoding influenza A hemagglutinin of the pandemic strain H1N1pdm09 as a model. This evaluation was performed using an in vitro model of human innate immunity and in vivo in mice after intradermal injection. Results suggest that immunostimulation from the mRNA vaccine in humans is similar to that in mice and acts through cellular RNA sensors, with genes for RLRs [ddx58 (RIG-1) and ifih1 (MDA-5)], TLRs (tlr3, tlr7, and tlr8-human only), and CLRs (clec4gp1, clec2d, cledl1) all significantly up-regulated by the mRNA vaccine. The up-regulation of TLR8 and TLR7 points to the involvement of both mDCs and pDCs in the response to the mRNA vaccine in humans. In both humans and mice activation of these pathways drove maturation and activation of immune cells as well as production of cytokines and chemokines known to attract and activate key players of the innate and adaptive immune system. This translational approach not only allowed for identification of the basic mechanisms of self-adjuvantation from the mRNA vaccine but also for comparison of the response across species, a response that appears relatively conserved or at least convergent between the in vitro human and in vivo mouse models.
      datePublished:2017-01-03T00:00:00Z
      dateModified:2017-01-03T00:00:00Z
      pageStart:1
      pageEnd:18
      license:http://creativecommons.org/publicdomain/zero/1.0/
      sameAs:https://doi.org/10.1186/s12967-016-1111-6
      keywords:
         mRNA
         Vaccine
         Innate
         In vitro
         MIMIC
         Adjuvant
         Human
         Mouse
         RLRs
         CLRs
         TLRs
         Self-adjuvantation
         Biomedicine
         general
         Medicine/Public Health
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      isPartOf:
         name:Journal of Translational Medicine
         issn:
            1479-5876
         volumeNumber:15
         type:
            Periodical
            PublicationVolume
      publisher:
         name:BioMed Central
         logo:
            url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
            type:ImageObject
         type:Organization
      author:
            name:Darin K. Edwards
            url:http://orcid.org/0000-0001-5977-6258
            affiliation:
                  name:Sanofi Pasteur, VaxDesign Campus
                  address:
                     name:Sanofi Pasteur, VaxDesign Campus, Orlando, USA
                     type:PostalAddress
                  type:Organization
            email:[email protected]
            type:Person
            name:Edith Jasny
            affiliation:
                  name:CureVac AG
                  address:
                     name:CureVac AG, Tübingen, Germany
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Heesik Yoon
            affiliation:
                  name:Sanofi Pasteur, VaxDesign Campus
                  address:
                     name:Sanofi Pasteur, VaxDesign Campus, Orlando, USA
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Nigel Horscroft
            affiliation:
                  name:CureVac AG
                  address:
                     name:CureVac AG, Tübingen, Germany
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Brian Schanen
            affiliation:
                  name:Sanofi Pasteur, VaxDesign Campus
                  address:
                     name:Sanofi Pasteur, VaxDesign Campus, Orlando, USA
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Tanya Geter
            affiliation:
                  name:Sanofi Pasteur, VaxDesign Campus
                  address:
                     name:Sanofi Pasteur, VaxDesign Campus, Orlando, USA
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Mariola Fotin-Mleczek
            affiliation:
                  name:CureVac AG
                  address:
                     name:CureVac AG, Tübingen, Germany
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Benjamin Petsch
            affiliation:
                  name:CureVac AG
                  address:
                     name:CureVac AG, Tübingen, Germany
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Vaughan Wittman
            affiliation:
                  name:Sanofi Pasteur, VaxDesign Campus
                  address:
                     name:Sanofi Pasteur, VaxDesign Campus, Orlando, USA
                     type:PostalAddress
                  type:Organization
            type:Person
      isAccessibleForFree:1
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      name:Journal of Translational Medicine
      issn:
         1479-5876
      volumeNumber:15
Organization:
      name:BioMed Central
      logo:
         url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
         type:ImageObject
      name:Sanofi Pasteur, VaxDesign Campus
      address:
         name:Sanofi Pasteur, VaxDesign Campus, Orlando, USA
         type:PostalAddress
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      address:
         name:CureVac AG, Tübingen, Germany
         type:PostalAddress
      name:Sanofi Pasteur, VaxDesign Campus
      address:
         name:Sanofi Pasteur, VaxDesign Campus, Orlando, USA
         type:PostalAddress
      name:CureVac AG
      address:
         name:CureVac AG, Tübingen, Germany
         type:PostalAddress
      name:Sanofi Pasteur, VaxDesign Campus
      address:
         name:Sanofi Pasteur, VaxDesign Campus, Orlando, USA
         type:PostalAddress
      name:Sanofi Pasteur, VaxDesign Campus
      address:
         name:Sanofi Pasteur, VaxDesign Campus, Orlando, USA
         type:PostalAddress
      name:CureVac AG
      address:
         name:CureVac AG, Tübingen, Germany
         type:PostalAddress
      name:CureVac AG
      address:
         name:CureVac AG, Tübingen, Germany
         type:PostalAddress
      name:Sanofi Pasteur, VaxDesign Campus
      address:
         name:Sanofi Pasteur, VaxDesign Campus, Orlando, USA
         type:PostalAddress
ImageObject:
      url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
Person:
      name:Darin K. Edwards
      url:http://orcid.org/0000-0001-5977-6258
      affiliation:
            name:Sanofi Pasteur, VaxDesign Campus
            address:
               name:Sanofi Pasteur, VaxDesign Campus, Orlando, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Edith Jasny
      affiliation:
            name:CureVac AG
            address:
               name:CureVac AG, Tübingen, Germany
               type:PostalAddress
            type:Organization
      name:Heesik Yoon
      affiliation:
            name:Sanofi Pasteur, VaxDesign Campus
            address:
               name:Sanofi Pasteur, VaxDesign Campus, Orlando, USA
               type:PostalAddress
            type:Organization
      name:Nigel Horscroft
      affiliation:
            name:CureVac AG
            address:
               name:CureVac AG, Tübingen, Germany
               type:PostalAddress
            type:Organization
      name:Brian Schanen
      affiliation:
            name:Sanofi Pasteur, VaxDesign Campus
            address:
               name:Sanofi Pasteur, VaxDesign Campus, Orlando, USA
               type:PostalAddress
            type:Organization
      name:Tanya Geter
      affiliation:
            name:Sanofi Pasteur, VaxDesign Campus
            address:
               name:Sanofi Pasteur, VaxDesign Campus, Orlando, USA
               type:PostalAddress
            type:Organization
      name:Mariola Fotin-Mleczek
      affiliation:
            name:CureVac AG
            address:
               name:CureVac AG, Tübingen, Germany
               type:PostalAddress
            type:Organization
      name:Benjamin Petsch
      affiliation:
            name:CureVac AG
            address:
               name:CureVac AG, Tübingen, Germany
               type:PostalAddress
            type:Organization
      name:Vaughan Wittman
      affiliation:
            name:Sanofi Pasteur, VaxDesign Campus
            address:
               name:Sanofi Pasteur, VaxDesign Campus, Orlando, USA
               type:PostalAddress
            type:Organization
PostalAddress:
      name:Sanofi Pasteur, VaxDesign Campus, Orlando, USA
      name:CureVac AG, Tübingen, Germany
      name:Sanofi Pasteur, VaxDesign Campus, Orlando, USA
      name:CureVac AG, Tübingen, Germany
      name:Sanofi Pasteur, VaxDesign Campus, Orlando, USA
      name:Sanofi Pasteur, VaxDesign Campus, Orlando, USA
      name:CureVac AG, Tübingen, Germany
      name:CureVac AG, Tübingen, Germany
      name:Sanofi Pasteur, VaxDesign Campus, Orlando, USA

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