Models Derived from <italic toggle="yes">In Vitro</italic> Analyses of Spleen, Liver, and Lung Leukocyte Functions Predict Vaccine Efficacy against the <named-content content-type="genus-species">Francisella tularensis</named-content> Live Vaccine Strain (LVS)

ABSTRACT Currently, there are no licensed vaccines and no correlates of protection against Francisella tularensis, which causes tularemia. We recently demonstrated that measuring in vitro control of intramacrophage bacterial growth by murine F. tularensis-immune splenocytes, as well as transcription...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Roberto De Pascalis, Alicia Y. Chou, Patrik Ryden, Nikki J. Kennett, Anders Sjöstedt, Karen L. Elkins
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5765e28e0d5d4a9591b63f0287921cd5
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5765e28e0d5d4a9591b63f0287921cd5
record_format	dspace
spelling	oai:doaj.org-article:5765e28e0d5d4a9591b63f0287921cd52021-11-15T15:45:13ZModels Derived from <italic toggle="yes">In Vitro</italic> Analyses of Spleen, Liver, and Lung Leukocyte Functions Predict Vaccine Efficacy against the <named-content content-type="genus-species">Francisella tularensis</named-content> Live Vaccine Strain (LVS)10.1128/mBio.00936-132150-7511https://doaj.org/article/5765e28e0d5d4a9591b63f0287921cd52014-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00936-13https://doaj.org/toc/2150-7511ABSTRACT Currently, there are no licensed vaccines and no correlates of protection against Francisella tularensis, which causes tularemia. We recently demonstrated that measuring in vitro control of intramacrophage bacterial growth by murine F. tularensis-immune splenocytes, as well as transcriptional analyses, discriminated Francisella vaccines of different efficacies. Further, we identified potential correlates of protection against systemic challenge. Here, we extended this approach by studying leukocytes derived from lungs and livers of mice immunized by parenteral and respiratory routes with F. tularensis vaccines. Liver and lung leukocytes derived from intradermally and intranasally vaccinated mice controlled in vitro Francisella Live Vaccine Strain (LVS) intramacrophage replication in patterns similar to those of splenocytes. Gene expression analyses of potential correlates also revealed similar patterns in liver cells and splenocytes. In some cases (e.g., tumor necrosis factor alpha [TNF-α], interleukin 22 [IL-22], and granulocyte-macrophage colony-stimulating factor [GM-CSF]), liver cells exhibited even higher relative gene expression, whereas fewer genes exhibited differential expression in lung cells. In contrast with their strong ability to control LVS replication, splenocytes from intranasally vaccinated mice expressed few genes with a hierarchy of expression similar to that of splenocytes from intradermally vaccinated mice. Thus, the relative levels of gene expression vary between cell types from different organs and by vaccination route. Most importantly, because studies comparing cell sources and routes of vaccination supported the predictive validity of this coculture and gene quantification approach, we combined in vitro LVS replication with gene expression data to develop analytical models that discriminated between vaccine groups and successfully predicted the degree of vaccine efficacy. Thus, this strategy remains a promising means of identifying and quantifying correlative T cell responses. IMPORTANCE Identifying and quantifying correlates of protection is especially challenging for intracellular bacteria, including Francisella tularensis. F. tularensis is classified as a category A bioterrorism agent, and no vaccines have been licensed in the United States, but tularemia is a rare disease. Therefore, clinical trials to test promising vaccines are impractical. In this report, we further evaluated a novel approach to developing correlates by assessing T cell immune responses in lungs and livers of differentially vaccinated mice; these nonprofessional immune tissues are colonized by Francisella. The relative degree of vaccine efficacy against systemic challenge was reflected by the ability of immune T cells, particularly liver T cells, to control the intramacrophage replication of bacteria in vitro and by relative gene expression of several immunological mediators. We therefore developed analytical models that combined bacterial replication data and gene expression data. Several resulting models provided excellent discrimination between vaccines of different efficacies.Roberto De PascalisAlicia Y. ChouPatrik RydenNikki J. KennettAnders SjöstedtKaren L. ElkinsAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 2 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Roberto De Pascalis Alicia Y. Chou Patrik Ryden Nikki J. Kennett Anders Sjöstedt Karen L. Elkins Models Derived from <italic toggle="yes">In Vitro</italic> Analyses of Spleen, Liver, and Lung Leukocyte Functions Predict Vaccine Efficacy against the <named-content content-type="genus-species">Francisella tularensis</named-content> Live Vaccine Strain (LVS)
description	ABSTRACT Currently, there are no licensed vaccines and no correlates of protection against Francisella tularensis, which causes tularemia. We recently demonstrated that measuring in vitro control of intramacrophage bacterial growth by murine F. tularensis-immune splenocytes, as well as transcriptional analyses, discriminated Francisella vaccines of different efficacies. Further, we identified potential correlates of protection against systemic challenge. Here, we extended this approach by studying leukocytes derived from lungs and livers of mice immunized by parenteral and respiratory routes with F. tularensis vaccines. Liver and lung leukocytes derived from intradermally and intranasally vaccinated mice controlled in vitro Francisella Live Vaccine Strain (LVS) intramacrophage replication in patterns similar to those of splenocytes. Gene expression analyses of potential correlates also revealed similar patterns in liver cells and splenocytes. In some cases (e.g., tumor necrosis factor alpha [TNF-α], interleukin 22 [IL-22], and granulocyte-macrophage colony-stimulating factor [GM-CSF]), liver cells exhibited even higher relative gene expression, whereas fewer genes exhibited differential expression in lung cells. In contrast with their strong ability to control LVS replication, splenocytes from intranasally vaccinated mice expressed few genes with a hierarchy of expression similar to that of splenocytes from intradermally vaccinated mice. Thus, the relative levels of gene expression vary between cell types from different organs and by vaccination route. Most importantly, because studies comparing cell sources and routes of vaccination supported the predictive validity of this coculture and gene quantification approach, we combined in vitro LVS replication with gene expression data to develop analytical models that discriminated between vaccine groups and successfully predicted the degree of vaccine efficacy. Thus, this strategy remains a promising means of identifying and quantifying correlative T cell responses. IMPORTANCE Identifying and quantifying correlates of protection is especially challenging for intracellular bacteria, including Francisella tularensis. F. tularensis is classified as a category A bioterrorism agent, and no vaccines have been licensed in the United States, but tularemia is a rare disease. Therefore, clinical trials to test promising vaccines are impractical. In this report, we further evaluated a novel approach to developing correlates by assessing T cell immune responses in lungs and livers of differentially vaccinated mice; these nonprofessional immune tissues are colonized by Francisella. The relative degree of vaccine efficacy against systemic challenge was reflected by the ability of immune T cells, particularly liver T cells, to control the intramacrophage replication of bacteria in vitro and by relative gene expression of several immunological mediators. We therefore developed analytical models that combined bacterial replication data and gene expression data. Several resulting models provided excellent discrimination between vaccines of different efficacies.
format	article
author	Roberto De Pascalis Alicia Y. Chou Patrik Ryden Nikki J. Kennett Anders Sjöstedt Karen L. Elkins
author_facet	Roberto De Pascalis Alicia Y. Chou Patrik Ryden Nikki J. Kennett Anders Sjöstedt Karen L. Elkins
author_sort	Roberto De Pascalis
title	Models Derived from <italic toggle="yes">In Vitro</italic> Analyses of Spleen, Liver, and Lung Leukocyte Functions Predict Vaccine Efficacy against the <named-content content-type="genus-species">Francisella tularensis</named-content> Live Vaccine Strain (LVS)
title_short	Models Derived from <italic toggle="yes">In Vitro</italic> Analyses of Spleen, Liver, and Lung Leukocyte Functions Predict Vaccine Efficacy against the <named-content content-type="genus-species">Francisella tularensis</named-content> Live Vaccine Strain (LVS)
title_full	Models Derived from <italic toggle="yes">In Vitro</italic> Analyses of Spleen, Liver, and Lung Leukocyte Functions Predict Vaccine Efficacy against the <named-content content-type="genus-species">Francisella tularensis</named-content> Live Vaccine Strain (LVS)
title_fullStr	Models Derived from <italic toggle="yes">In Vitro</italic> Analyses of Spleen, Liver, and Lung Leukocyte Functions Predict Vaccine Efficacy against the <named-content content-type="genus-species">Francisella tularensis</named-content> Live Vaccine Strain (LVS)
title_full_unstemmed	Models Derived from <italic toggle="yes">In Vitro</italic> Analyses of Spleen, Liver, and Lung Leukocyte Functions Predict Vaccine Efficacy against the <named-content content-type="genus-species">Francisella tularensis</named-content> Live Vaccine Strain (LVS)
title_sort	models derived from <italic toggle="yes">in vitro</italic> analyses of spleen, liver, and lung leukocyte functions predict vaccine efficacy against the <named-content content-type="genus-species">francisella tularensis</named-content> live vaccine strain (lvs)
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/5765e28e0d5d4a9591b63f0287921cd5
work_keys_str_mv	AT robertodepascalis modelsderivedfromitalictoggleyesinvitroitalicanalysesofspleenliverandlungleukocytefunctionspredictvaccineefficacyagainstthenamedcontentcontenttypegenusspeciesfrancisellatularensisnamedcontentlivevaccinestrainlvs AT aliciaychou modelsderivedfromitalictoggleyesinvitroitalicanalysesofspleenliverandlungleukocytefunctionspredictvaccineefficacyagainstthenamedcontentcontenttypegenusspeciesfrancisellatularensisnamedcontentlivevaccinestrainlvs AT patrikryden modelsderivedfromitalictoggleyesinvitroitalicanalysesofspleenliverandlungleukocytefunctionspredictvaccineefficacyagainstthenamedcontentcontenttypegenusspeciesfrancisellatularensisnamedcontentlivevaccinestrainlvs AT nikkijkennett modelsderivedfromitalictoggleyesinvitroitalicanalysesofspleenliverandlungleukocytefunctionspredictvaccineefficacyagainstthenamedcontentcontenttypegenusspeciesfrancisellatularensisnamedcontentlivevaccinestrainlvs AT anderssjostedt modelsderivedfromitalictoggleyesinvitroitalicanalysesofspleenliverandlungleukocytefunctionspredictvaccineefficacyagainstthenamedcontentcontenttypegenusspeciesfrancisellatularensisnamedcontentlivevaccinestrainlvs AT karenlelkins modelsderivedfromitalictoggleyesinvitroitalicanalysesofspleenliverandlungleukocytefunctionspredictvaccineefficacyagainstthenamedcontentcontenttypegenusspeciesfrancisellatularensisnamedcontentlivevaccinestrainlvs
_version_	1718427584992116736

Models Derived from <italic toggle="yes">In Vitro</italic> Analyses of Spleen, Liver, and Lung Leukocyte Functions Predict Vaccine Efficacy against the <named-content content-type="genus-species">Francisella tularensis</named-content> Live Vaccine Strain (LVS)

Ejemplares similares