Transcriptomics in human challenge models

Human challenge models, in which volunteers are experimentally infected with a pathogen of interest, provide the opportunity to directly identify both natural and vaccine-induced correlates of protection. In this review, we highlight how the applica tion of transcriptomics to human challenge studies...

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Main Authors: Barton, A, Hill, J, Pollard, A, Blohmke, C
Format: Journal article
Published: Frontiers Media 2017
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author Barton, A
Hill, J
Pollard, A
Blohmke, C
author_facet Barton, A
Hill, J
Pollard, A
Blohmke, C
author_sort Barton, A
collection OXFORD
description Human challenge models, in which volunteers are experimentally infected with a pathogen of interest, provide the opportunity to directly identify both natural and vaccine-induced correlates of protection. In this review, we highlight how the applica tion of transcriptomics to human challenge studies allows for the identification of novel correlates and gives insight into the immunological pathways required to develop functional immunity. In malaria challenge trials for example, innate immune pathways appear to play a previously underappreciated role in conferring protective immunity. Transcriptomic analyses of samples obtained in human challenge studies can also deepen our understanding of the immune responses preceding symptom onset, allowing characterization of innate immunity and early gene signatures, which may influence disease outcome. Influenza challenge studies demonstrate that these gene signatures have diagnostic potential in the context of pandemics, in which presymptomatic diagnosis of at-risk individuals could allow early initiation of antiviral treatment and help limit transmission. Furthermore, gene expression analysis facilitates the identification of host factors contributing to disease susceptibility, such as C4BPA expression in enterotoxigenic Escherichia coli infection. Overall, these studies highlight the exceptional value of transcriptional data generated in human challenge trials and illustrate the broad impact molecular data analysis may have on global health through rational vaccine design and biomarker discovery.
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spelling oxford-uuid:ca98e488-162c-4cbf-a2be-6985bfce9ae52022-03-27T07:08:34ZTranscriptomics in human challenge modelsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ca98e488-162c-4cbf-a2be-6985bfce9ae5Symplectic Elements at OxfordFrontiers Media2017Barton, AHill, JPollard, ABlohmke, CHuman challenge models, in which volunteers are experimentally infected with a pathogen of interest, provide the opportunity to directly identify both natural and vaccine-induced correlates of protection. In this review, we highlight how the applica tion of transcriptomics to human challenge studies allows for the identification of novel correlates and gives insight into the immunological pathways required to develop functional immunity. In malaria challenge trials for example, innate immune pathways appear to play a previously underappreciated role in conferring protective immunity. Transcriptomic analyses of samples obtained in human challenge studies can also deepen our understanding of the immune responses preceding symptom onset, allowing characterization of innate immunity and early gene signatures, which may influence disease outcome. Influenza challenge studies demonstrate that these gene signatures have diagnostic potential in the context of pandemics, in which presymptomatic diagnosis of at-risk individuals could allow early initiation of antiviral treatment and help limit transmission. Furthermore, gene expression analysis facilitates the identification of host factors contributing to disease susceptibility, such as C4BPA expression in enterotoxigenic Escherichia coli infection. Overall, these studies highlight the exceptional value of transcriptional data generated in human challenge trials and illustrate the broad impact molecular data analysis may have on global health through rational vaccine design and biomarker discovery.
spellingShingle Barton, A
Hill, J
Pollard, A
Blohmke, C
Transcriptomics in human challenge models
title Transcriptomics in human challenge models
title_full Transcriptomics in human challenge models
title_fullStr Transcriptomics in human challenge models
title_full_unstemmed Transcriptomics in human challenge models
title_short Transcriptomics in human challenge models
title_sort transcriptomics in human challenge models
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AT hillj transcriptomicsinhumanchallengemodels
AT pollarda transcriptomicsinhumanchallengemodels
AT blohmkec transcriptomicsinhumanchallengemodels