Immunization of mice with lentiviral vectors targeted to MHC class II+ cells is due to preferential transduction of dendritic cells in vivo.

Gene transfer vectors such as lentiviral vectors offer versatile possibilities to express transgenic antigens for vaccination purposes. However, viral vaccines leading to broad transduction and transgene expression in vivo, are undesirable. Therefore, strategies capable of directing gene transfer on...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Séverine Ciré, Sylvie Da Rocha, Roseline Yao, Sylvain Fisson, Christian J Buchholz, Mary K Collins, Anne Galy
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/92971d21e25243fbbeac7990ed174be4
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:92971d21e25243fbbeac7990ed174be4
record_format	dspace
spelling	oai:doaj.org-article:92971d21e25243fbbeac7990ed174be42021-11-25T06:07:16ZImmunization of mice with lentiviral vectors targeted to MHC class II+ cells is due to preferential transduction of dendritic cells in vivo.1932-620310.1371/journal.pone.0101644https://doaj.org/article/92971d21e25243fbbeac7990ed174be42014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25058148/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Gene transfer vectors such as lentiviral vectors offer versatile possibilities to express transgenic antigens for vaccination purposes. However, viral vaccines leading to broad transduction and transgene expression in vivo, are undesirable. Therefore, strategies capable of directing gene transfer only to professional antigen-presenting cells would increase the specific activity and safety of genetic vaccines. A lentiviral vector pseudotype specific for murine major histocompatibilty complex class II (LV-MHCII) was recently developed and the present study aims to characterize the in vivo biodistribution profile and immunization potential of this vector in mice. Whereas the systemic administration of a vector pseudotyped with a ubiquitously-interacting envelope led to prominent detection of vector copies in the liver of animals, the injection of an equivalent amount of LV-MHCII resulted in a more specific biodistribution of vector and transgene. Copies of LV-MHCII were found only in secondary lymphoid organs, essentially in CD11c+ dendritic cells expressing the transgene whereas B cells were not efficiently targeted in vivo, contrary to expectations based on in vitro testing. Upon a single injection of LV-MHCII, naive mice mounted specific effector CD4 and CD8 T cell responses against the intracelllular transgene product with the generation of Th1 cytokines, development of in vivo cytotoxic activity and establishment of T cell immune memory. The targeting of dendritic cells by recombinant viral vaccines must therefore be assessed in vivo but this strategy is feasible, effective for immunization and cross-presentation and constitutes a potentially safe alternative to limit off-target gene expression in gene-based vaccination strategies with integrative vectors.Séverine CiréSylvie Da RochaRoseline YaoSylvain FissonChristian J BuchholzMary K CollinsAnne GalyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e101644 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Séverine Ciré Sylvie Da Rocha Roseline Yao Sylvain Fisson Christian J Buchholz Mary K Collins Anne Galy Immunization of mice with lentiviral vectors targeted to MHC class II+ cells is due to preferential transduction of dendritic cells in vivo.
description	Gene transfer vectors such as lentiviral vectors offer versatile possibilities to express transgenic antigens for vaccination purposes. However, viral vaccines leading to broad transduction and transgene expression in vivo, are undesirable. Therefore, strategies capable of directing gene transfer only to professional antigen-presenting cells would increase the specific activity and safety of genetic vaccines. A lentiviral vector pseudotype specific for murine major histocompatibilty complex class II (LV-MHCII) was recently developed and the present study aims to characterize the in vivo biodistribution profile and immunization potential of this vector in mice. Whereas the systemic administration of a vector pseudotyped with a ubiquitously-interacting envelope led to prominent detection of vector copies in the liver of animals, the injection of an equivalent amount of LV-MHCII resulted in a more specific biodistribution of vector and transgene. Copies of LV-MHCII were found only in secondary lymphoid organs, essentially in CD11c+ dendritic cells expressing the transgene whereas B cells were not efficiently targeted in vivo, contrary to expectations based on in vitro testing. Upon a single injection of LV-MHCII, naive mice mounted specific effector CD4 and CD8 T cell responses against the intracelllular transgene product with the generation of Th1 cytokines, development of in vivo cytotoxic activity and establishment of T cell immune memory. The targeting of dendritic cells by recombinant viral vaccines must therefore be assessed in vivo but this strategy is feasible, effective for immunization and cross-presentation and constitutes a potentially safe alternative to limit off-target gene expression in gene-based vaccination strategies with integrative vectors.
format	article
author	Séverine Ciré Sylvie Da Rocha Roseline Yao Sylvain Fisson Christian J Buchholz Mary K Collins Anne Galy
author_facet	Séverine Ciré Sylvie Da Rocha Roseline Yao Sylvain Fisson Christian J Buchholz Mary K Collins Anne Galy
author_sort	Séverine Ciré
title	Immunization of mice with lentiviral vectors targeted to MHC class II+ cells is due to preferential transduction of dendritic cells in vivo.
title_short	Immunization of mice with lentiviral vectors targeted to MHC class II+ cells is due to preferential transduction of dendritic cells in vivo.
title_full	Immunization of mice with lentiviral vectors targeted to MHC class II+ cells is due to preferential transduction of dendritic cells in vivo.
title_fullStr	Immunization of mice with lentiviral vectors targeted to MHC class II+ cells is due to preferential transduction of dendritic cells in vivo.
title_full_unstemmed	Immunization of mice with lentiviral vectors targeted to MHC class II+ cells is due to preferential transduction of dendritic cells in vivo.
title_sort	immunization of mice with lentiviral vectors targeted to mhc class ii+ cells is due to preferential transduction of dendritic cells in vivo.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/92971d21e25243fbbeac7990ed174be4
work_keys_str_mv	AT severinecire immunizationofmicewithlentiviralvectorstargetedtomhcclassiicellsisduetopreferentialtransductionofdendriticcellsinvivo AT sylviedarocha immunizationofmicewithlentiviralvectorstargetedtomhcclassiicellsisduetopreferentialtransductionofdendriticcellsinvivo AT roselineyao immunizationofmicewithlentiviralvectorstargetedtomhcclassiicellsisduetopreferentialtransductionofdendriticcellsinvivo AT sylvainfisson immunizationofmicewithlentiviralvectorstargetedtomhcclassiicellsisduetopreferentialtransductionofdendriticcellsinvivo AT christianjbuchholz immunizationofmicewithlentiviralvectorstargetedtomhcclassiicellsisduetopreferentialtransductionofdendriticcellsinvivo AT marykcollins immunizationofmicewithlentiviralvectorstargetedtomhcclassiicellsisduetopreferentialtransductionofdendriticcellsinvivo AT annegaly immunizationofmicewithlentiviralvectorstargetedtomhcclassiicellsisduetopreferentialtransductionofdendriticcellsinvivo
_version_	1718414176268845056

Immunization of mice with lentiviral vectors targeted to MHC class II+ cells is due to preferential transduction of dendritic cells in vivo.

Ejemplares similares