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Transcriptomic Profiles of High and Low Antibody Responders to Smallpox Vaccine

Despite its eradication over 30 years ago, smallpox (as well as other orthopoxviruses) remains a pathogen of interest both in terms of biodefense and for its use as a vector for vaccines and immunotherapies. Here we describe the application of mRNA-Seq transcriptome profiling to understanding immune...

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Autores principales: Kennedy, Richard B., Oberg, Ann L., Ovsyannikova, Inna G., Haralambieva, Iana H., Grill, Diane, Poland, Gregory A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3723701/
https://www.ncbi.nlm.nih.gov/pubmed/23594957
http://dx.doi.org/10.1038/gene.2013.14
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author Kennedy, Richard B.
Oberg, Ann L.
Ovsyannikova, Inna G.
Haralambieva, Iana H.
Grill, Diane
Poland, Gregory A.
author_facet Kennedy, Richard B.
Oberg, Ann L.
Ovsyannikova, Inna G.
Haralambieva, Iana H.
Grill, Diane
Poland, Gregory A.
author_sort Kennedy, Richard B.
collection PubMed
description Despite its eradication over 30 years ago, smallpox (as well as other orthopoxviruses) remains a pathogen of interest both in terms of biodefense and for its use as a vector for vaccines and immunotherapies. Here we describe the application of mRNA-Seq transcriptome profiling to understanding immune responses in smallpox vaccine recipients. Contrary to other studies examining gene expression in virally infected cell lines, we utilized a mixed population of PBMCs in order to capture the essential intercellular interactions that occur in vivo and would otherwise be lost using single cell lines or isolated primary cell subsets. In this mixed cell population we were able to detect expression of all annotated vaccinia genes. On the host side, a number of genes encoding cytokines, chemokines, complement factors, and intracellular signaling molecules were downregulated upon viral infection, while genes encoding histone proteins and the interferon response were upregulated. We also identified a small number of genes that exhibited significantly different expression profiles in subjects with robust humoral immunity compared to those with weaker humoral responses. Our results provide evidence that differential gene regulation patterns may be at work in individuals with robust humoral immunity compared to those with weaker humoral immune responses.
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spelling pubmed-37237012014-01-01 Transcriptomic Profiles of High and Low Antibody Responders to Smallpox Vaccine Kennedy, Richard B. Oberg, Ann L. Ovsyannikova, Inna G. Haralambieva, Iana H. Grill, Diane Poland, Gregory A. Genes Immun Article Despite its eradication over 30 years ago, smallpox (as well as other orthopoxviruses) remains a pathogen of interest both in terms of biodefense and for its use as a vector for vaccines and immunotherapies. Here we describe the application of mRNA-Seq transcriptome profiling to understanding immune responses in smallpox vaccine recipients. Contrary to other studies examining gene expression in virally infected cell lines, we utilized a mixed population of PBMCs in order to capture the essential intercellular interactions that occur in vivo and would otherwise be lost using single cell lines or isolated primary cell subsets. In this mixed cell population we were able to detect expression of all annotated vaccinia genes. On the host side, a number of genes encoding cytokines, chemokines, complement factors, and intracellular signaling molecules were downregulated upon viral infection, while genes encoding histone proteins and the interferon response were upregulated. We also identified a small number of genes that exhibited significantly different expression profiles in subjects with robust humoral immunity compared to those with weaker humoral responses. Our results provide evidence that differential gene regulation patterns may be at work in individuals with robust humoral immunity compared to those with weaker humoral immune responses. 2013-04-18 2013 /pmc/articles/PMC3723701/ /pubmed/23594957 http://dx.doi.org/10.1038/gene.2013.14 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Kennedy, Richard B.
Oberg, Ann L.
Ovsyannikova, Inna G.
Haralambieva, Iana H.
Grill, Diane
Poland, Gregory A.
Transcriptomic Profiles of High and Low Antibody Responders to Smallpox Vaccine
title Transcriptomic Profiles of High and Low Antibody Responders to Smallpox Vaccine
title_full Transcriptomic Profiles of High and Low Antibody Responders to Smallpox Vaccine
title_fullStr Transcriptomic Profiles of High and Low Antibody Responders to Smallpox Vaccine
title_full_unstemmed Transcriptomic Profiles of High and Low Antibody Responders to Smallpox Vaccine
title_short Transcriptomic Profiles of High and Low Antibody Responders to Smallpox Vaccine
title_sort transcriptomic profiles of high and low antibody responders to smallpox vaccine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3723701/
https://www.ncbi.nlm.nih.gov/pubmed/23594957
http://dx.doi.org/10.1038/gene.2013.14
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