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Six host-range restricted poxviruses from three genera induce distinct gene expression profiles in an in vivo mouse model

BACKGROUND: Host-range restricted poxviruses make promising vaccine vectors due to their safety profile and immunogenicity. An understanding of the host innate immune responses produced by different poxvirus vectors would aid in the assessment, selection and rational design of improved vaccines for...

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Autores principales: Offerman, Kristy, Deffur, Armin, Carulei, Olivia, Wilkinson, Robert, Douglass, Nicola, Williamson, Anna-Lise
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495948/
https://www.ncbi.nlm.nih.gov/pubmed/26153454
http://dx.doi.org/10.1186/s12864-015-1659-1
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author Offerman, Kristy
Deffur, Armin
Carulei, Olivia
Wilkinson, Robert
Douglass, Nicola
Williamson, Anna-Lise
author_facet Offerman, Kristy
Deffur, Armin
Carulei, Olivia
Wilkinson, Robert
Douglass, Nicola
Williamson, Anna-Lise
author_sort Offerman, Kristy
collection PubMed
description BACKGROUND: Host-range restricted poxviruses make promising vaccine vectors due to their safety profile and immunogenicity. An understanding of the host innate immune responses produced by different poxvirus vectors would aid in the assessment, selection and rational design of improved vaccines for human and veterinary applications. Novel avipoxviruses are being assessed to determine if they are different from other poxvirus vectors. Analysis of the transcriptome induced in a mouse model would aid in determining if there were significant differences between different poxvirus vectors which may reflect different adjuvant potential as well as establish if they should be further evaluated as vaccine vectors. RESULTS: We compared host transcript abundance in the spleens of BALB/c mice twenty four hours after intravenous infection (10(5) pfu/mouse) with six host-restricted poxvirus species from three genera, namely Lumpy Skin Disease virus (LSDV), Canarypox virus (CNPV), Fowlpox virus (FWPV), modified vaccinia Ankara (MVA) and two novel South African avipoxviruses, Feral Pigeonpox virus (FeP2) and Penguinpox virus (PEPV). These six viruses produced qualitatively and quantitatively distinct host responses with LSDV, followed by MVA, inducing the greatest interferon (IFN) response. FeP2 and PEPV caused very little change to host transcript abundance compared to the other 4 viruses tested. CNPV and FWPV induced the up regulation of two immunoglobulin genes (Ighg and Ighg3 (IgG3)) with CNPV inducing a third, Ighm (IgM). HIV-1–specific IgG3 antibodies have been correlated with decreased risk of HIV-1 infection in the RV144 trial, which included a CNPV-based vector (Yates et al. (Sci Transl Med, 6(228) p228, 2014). Up regulation of IgG3 by CNPV and FWPV but not the other poxviruses tested in vivo, implies that these two avipoxvirus-vector backbones may be involved in stimulation of the clinically important IgG3 antibody subclass. Differential transcript abundance associated with the different poxviruses is further discussed with particular emphasis on responses related to immune responses. CONCLUSION: Six, genetically diverse host-restricted poxviruses produce different responses in a mouse model early after infection. These differences may affect the immune response induced to vaccine antigen in vectors based on these viruses. The two novel avipoxviruses were clearly distinguishable from the other viruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1659-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-44959482015-07-09 Six host-range restricted poxviruses from three genera induce distinct gene expression profiles in an in vivo mouse model Offerman, Kristy Deffur, Armin Carulei, Olivia Wilkinson, Robert Douglass, Nicola Williamson, Anna-Lise BMC Genomics Research Article BACKGROUND: Host-range restricted poxviruses make promising vaccine vectors due to their safety profile and immunogenicity. An understanding of the host innate immune responses produced by different poxvirus vectors would aid in the assessment, selection and rational design of improved vaccines for human and veterinary applications. Novel avipoxviruses are being assessed to determine if they are different from other poxvirus vectors. Analysis of the transcriptome induced in a mouse model would aid in determining if there were significant differences between different poxvirus vectors which may reflect different adjuvant potential as well as establish if they should be further evaluated as vaccine vectors. RESULTS: We compared host transcript abundance in the spleens of BALB/c mice twenty four hours after intravenous infection (10(5) pfu/mouse) with six host-restricted poxvirus species from three genera, namely Lumpy Skin Disease virus (LSDV), Canarypox virus (CNPV), Fowlpox virus (FWPV), modified vaccinia Ankara (MVA) and two novel South African avipoxviruses, Feral Pigeonpox virus (FeP2) and Penguinpox virus (PEPV). These six viruses produced qualitatively and quantitatively distinct host responses with LSDV, followed by MVA, inducing the greatest interferon (IFN) response. FeP2 and PEPV caused very little change to host transcript abundance compared to the other 4 viruses tested. CNPV and FWPV induced the up regulation of two immunoglobulin genes (Ighg and Ighg3 (IgG3)) with CNPV inducing a third, Ighm (IgM). HIV-1–specific IgG3 antibodies have been correlated with decreased risk of HIV-1 infection in the RV144 trial, which included a CNPV-based vector (Yates et al. (Sci Transl Med, 6(228) p228, 2014). Up regulation of IgG3 by CNPV and FWPV but not the other poxviruses tested in vivo, implies that these two avipoxvirus-vector backbones may be involved in stimulation of the clinically important IgG3 antibody subclass. Differential transcript abundance associated with the different poxviruses is further discussed with particular emphasis on responses related to immune responses. CONCLUSION: Six, genetically diverse host-restricted poxviruses produce different responses in a mouse model early after infection. These differences may affect the immune response induced to vaccine antigen in vectors based on these viruses. The two novel avipoxviruses were clearly distinguishable from the other viruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1659-1) contains supplementary material, which is available to authorized users. BioMed Central 2015-07-08 /pmc/articles/PMC4495948/ /pubmed/26153454 http://dx.doi.org/10.1186/s12864-015-1659-1 Text en © Offerman et al. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Offerman, Kristy
Deffur, Armin
Carulei, Olivia
Wilkinson, Robert
Douglass, Nicola
Williamson, Anna-Lise
Six host-range restricted poxviruses from three genera induce distinct gene expression profiles in an in vivo mouse model
title Six host-range restricted poxviruses from three genera induce distinct gene expression profiles in an in vivo mouse model
title_full Six host-range restricted poxviruses from three genera induce distinct gene expression profiles in an in vivo mouse model
title_fullStr Six host-range restricted poxviruses from three genera induce distinct gene expression profiles in an in vivo mouse model
title_full_unstemmed Six host-range restricted poxviruses from three genera induce distinct gene expression profiles in an in vivo mouse model
title_short Six host-range restricted poxviruses from three genera induce distinct gene expression profiles in an in vivo mouse model
title_sort six host-range restricted poxviruses from three genera induce distinct gene expression profiles in an in vivo mouse model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495948/
https://www.ncbi.nlm.nih.gov/pubmed/26153454
http://dx.doi.org/10.1186/s12864-015-1659-1
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