Sustained Liver HBsAg Loss and Clonal T- and B-Cell Expansion upon Therapeutic DNA Vaccination Require Low HBsAg Levels

Background: Suppression of HBV DNA, inhibition of HBV surface (HBsAg) production and therapeutic vaccination to reverse HBV-specific T-cell exhaustion in chronic HBV patients are likely required to achieve a functional cure. In the AAV-HBV mouse model, therapeutic vaccination can be effective in cle...
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Autor*in:	Nádia Conceição-Neto [verfasserIn] Wim Pierson [verfasserIn] Maurizio Vacca [verfasserIn] Matthias Beyens [verfasserIn] Ben De Clerck [verfasserIn] Liese Aerts [verfasserIn] Birgit Voeten [verfasserIn] Dorien De Pooter [verfasserIn] Lore Verschueren [verfasserIn] Koen Dockx [verfasserIn] Mathias Vandenberk [verfasserIn] Ewoud De Troyer [verfasserIn] Kato Verwilt [verfasserIn] Carl Van Hove [verfasserIn] Mieke Verslegers [verfasserIn] Leslie Bosseler [verfasserIn] Marjolein Crabbe [verfasserIn] Vinod Krishna [verfasserIn] Isabel Nájera [verfasserIn] Ellen Van Gulck [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	HBV single-cell-RNA sequencing liver cytotoxic CD8 T cells CD4 follicular helper T cells vaccine

Übergeordnetes Werk:	In: Vaccines - MDPI AG, 2013, 11(2023), 12, p 1825
Übergeordnetes Werk:	volume:11 ; year:2023 ; number:12, p 1825

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/vaccines11121825

Katalog-ID:	DOAJ098785559

Internformat


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allfields	10.3390/vaccines11121825 doi (DE-627)DOAJ098785559 (DE-599)DOAJ02d6e9e3b591445ea06f0b781cc5a5c2 DE-627 ger DE-627 rakwb eng Nádia Conceição-Neto verfasserin aut Sustained Liver HBsAg Loss and Clonal T- and B-Cell Expansion upon Therapeutic DNA Vaccination Require Low HBsAg Levels 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Suppression of HBV DNA, inhibition of HBV surface (HBsAg) production and therapeutic vaccination to reverse HBV-specific T-cell exhaustion in chronic HBV patients are likely required to achieve a functional cure. In the AAV-HBV mouse model, therapeutic vaccination can be effective in clearing HBV when HBsAg levels are low. Using a single-cell approach, we investigated the liver immune environment with different levels of HBsAg and sustained HBsAg loss through treatment with a GalNAc-HBV-siRNA followed by therapeutic vaccination. Methods: AAV-HBV-transduced C57BL/6 mice were treated with GalNAc-HBV-siRNA to lower HBsAg levels and then vaccinated using a DNA vaccine. We used single-cell RNA and V(D)J sequencing to understand liver immune microenvironment changes. Results: GalNAc-HBV-siRNA, followed by therapeutic vaccination, achieved sustained HBsAg loss in all mice. This was accompanied by CD4 follicular helper T-cell induction, polyclonal activation of CD8 T cells and clonal expansion of plasma cells that were responsible for antibody production. Conclusions: This study provides novel insights into liver immune changes at the single-cell level, highlighting the correlation between induced reduction of HBsAg levels and clonal expansion of CD4, CD8 T cells and plasma cells in the liver upon HBV siRNA and subsequent therapeutic vaccination. HBV single-cell-RNA sequencing liver cytotoxic CD8 T cells CD4 follicular helper T cells vaccine Medicine R Wim Pierson verfasserin aut Maurizio Vacca verfasserin aut Matthias Beyens verfasserin aut Ben De Clerck verfasserin aut Liese Aerts verfasserin aut Birgit Voeten verfasserin aut Dorien De Pooter verfasserin aut Lore Verschueren verfasserin aut Koen Dockx verfasserin aut Mathias Vandenberk verfasserin aut Ewoud De Troyer verfasserin aut Kato Verwilt verfasserin aut Carl Van Hove verfasserin aut Mieke Verslegers verfasserin aut Leslie Bosseler verfasserin aut Marjolein Crabbe verfasserin aut Vinod Krishna verfasserin aut Isabel Nájera verfasserin aut Ellen Van Gulck verfasserin aut In Vaccines MDPI AG, 2013 11(2023), 12, p 1825 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:11 year:2023 number:12, p 1825 https://doi.org/10.3390/vaccines11121825 kostenfrei https://doaj.org/article/02d6e9e3b591445ea06f0b781cc5a5c2 kostenfrei https://www.mdpi.com/2076-393X/11/12/1825 kostenfrei https://doaj.org/toc/2076-393X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2023 12, p 1825
spelling	10.3390/vaccines11121825 doi (DE-627)DOAJ098785559 (DE-599)DOAJ02d6e9e3b591445ea06f0b781cc5a5c2 DE-627 ger DE-627 rakwb eng Nádia Conceição-Neto verfasserin aut Sustained Liver HBsAg Loss and Clonal T- and B-Cell Expansion upon Therapeutic DNA Vaccination Require Low HBsAg Levels 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Suppression of HBV DNA, inhibition of HBV surface (HBsAg) production and therapeutic vaccination to reverse HBV-specific T-cell exhaustion in chronic HBV patients are likely required to achieve a functional cure. In the AAV-HBV mouse model, therapeutic vaccination can be effective in clearing HBV when HBsAg levels are low. Using a single-cell approach, we investigated the liver immune environment with different levels of HBsAg and sustained HBsAg loss through treatment with a GalNAc-HBV-siRNA followed by therapeutic vaccination. Methods: AAV-HBV-transduced C57BL/6 mice were treated with GalNAc-HBV-siRNA to lower HBsAg levels and then vaccinated using a DNA vaccine. We used single-cell RNA and V(D)J sequencing to understand liver immune microenvironment changes. Results: GalNAc-HBV-siRNA, followed by therapeutic vaccination, achieved sustained HBsAg loss in all mice. This was accompanied by CD4 follicular helper T-cell induction, polyclonal activation of CD8 T cells and clonal expansion of plasma cells that were responsible for antibody production. Conclusions: This study provides novel insights into liver immune changes at the single-cell level, highlighting the correlation between induced reduction of HBsAg levels and clonal expansion of CD4, CD8 T cells and plasma cells in the liver upon HBV siRNA and subsequent therapeutic vaccination. HBV single-cell-RNA sequencing liver cytotoxic CD8 T cells CD4 follicular helper T cells vaccine Medicine R Wim Pierson verfasserin aut Maurizio Vacca verfasserin aut Matthias Beyens verfasserin aut Ben De Clerck verfasserin aut Liese Aerts verfasserin aut Birgit Voeten verfasserin aut Dorien De Pooter verfasserin aut Lore Verschueren verfasserin aut Koen Dockx verfasserin aut Mathias Vandenberk verfasserin aut Ewoud De Troyer verfasserin aut Kato Verwilt verfasserin aut Carl Van Hove verfasserin aut Mieke Verslegers verfasserin aut Leslie Bosseler verfasserin aut Marjolein Crabbe verfasserin aut Vinod Krishna verfasserin aut Isabel Nájera verfasserin aut Ellen Van Gulck verfasserin aut In Vaccines MDPI AG, 2013 11(2023), 12, p 1825 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:11 year:2023 number:12, p 1825 https://doi.org/10.3390/vaccines11121825 kostenfrei https://doaj.org/article/02d6e9e3b591445ea06f0b781cc5a5c2 kostenfrei https://www.mdpi.com/2076-393X/11/12/1825 kostenfrei https://doaj.org/toc/2076-393X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2023 12, p 1825
allfields_unstemmed	10.3390/vaccines11121825 doi (DE-627)DOAJ098785559 (DE-599)DOAJ02d6e9e3b591445ea06f0b781cc5a5c2 DE-627 ger DE-627 rakwb eng Nádia Conceição-Neto verfasserin aut Sustained Liver HBsAg Loss and Clonal T- and B-Cell Expansion upon Therapeutic DNA Vaccination Require Low HBsAg Levels 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Suppression of HBV DNA, inhibition of HBV surface (HBsAg) production and therapeutic vaccination to reverse HBV-specific T-cell exhaustion in chronic HBV patients are likely required to achieve a functional cure. In the AAV-HBV mouse model, therapeutic vaccination can be effective in clearing HBV when HBsAg levels are low. Using a single-cell approach, we investigated the liver immune environment with different levels of HBsAg and sustained HBsAg loss through treatment with a GalNAc-HBV-siRNA followed by therapeutic vaccination. Methods: AAV-HBV-transduced C57BL/6 mice were treated with GalNAc-HBV-siRNA to lower HBsAg levels and then vaccinated using a DNA vaccine. We used single-cell RNA and V(D)J sequencing to understand liver immune microenvironment changes. Results: GalNAc-HBV-siRNA, followed by therapeutic vaccination, achieved sustained HBsAg loss in all mice. This was accompanied by CD4 follicular helper T-cell induction, polyclonal activation of CD8 T cells and clonal expansion of plasma cells that were responsible for antibody production. Conclusions: This study provides novel insights into liver immune changes at the single-cell level, highlighting the correlation between induced reduction of HBsAg levels and clonal expansion of CD4, CD8 T cells and plasma cells in the liver upon HBV siRNA and subsequent therapeutic vaccination. HBV single-cell-RNA sequencing liver cytotoxic CD8 T cells CD4 follicular helper T cells vaccine Medicine R Wim Pierson verfasserin aut Maurizio Vacca verfasserin aut Matthias Beyens verfasserin aut Ben De Clerck verfasserin aut Liese Aerts verfasserin aut Birgit Voeten verfasserin aut Dorien De Pooter verfasserin aut Lore Verschueren verfasserin aut Koen Dockx verfasserin aut Mathias Vandenberk verfasserin aut Ewoud De Troyer verfasserin aut Kato Verwilt verfasserin aut Carl Van Hove verfasserin aut Mieke Verslegers verfasserin aut Leslie Bosseler verfasserin aut Marjolein Crabbe verfasserin aut Vinod Krishna verfasserin aut Isabel Nájera verfasserin aut Ellen Van Gulck verfasserin aut In Vaccines MDPI AG, 2013 11(2023), 12, p 1825 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:11 year:2023 number:12, p 1825 https://doi.org/10.3390/vaccines11121825 kostenfrei https://doaj.org/article/02d6e9e3b591445ea06f0b781cc5a5c2 kostenfrei https://www.mdpi.com/2076-393X/11/12/1825 kostenfrei https://doaj.org/toc/2076-393X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2023 12, p 1825
allfieldsGer	10.3390/vaccines11121825 doi (DE-627)DOAJ098785559 (DE-599)DOAJ02d6e9e3b591445ea06f0b781cc5a5c2 DE-627 ger DE-627 rakwb eng Nádia Conceição-Neto verfasserin aut Sustained Liver HBsAg Loss and Clonal T- and B-Cell Expansion upon Therapeutic DNA Vaccination Require Low HBsAg Levels 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Suppression of HBV DNA, inhibition of HBV surface (HBsAg) production and therapeutic vaccination to reverse HBV-specific T-cell exhaustion in chronic HBV patients are likely required to achieve a functional cure. In the AAV-HBV mouse model, therapeutic vaccination can be effective in clearing HBV when HBsAg levels are low. Using a single-cell approach, we investigated the liver immune environment with different levels of HBsAg and sustained HBsAg loss through treatment with a GalNAc-HBV-siRNA followed by therapeutic vaccination. Methods: AAV-HBV-transduced C57BL/6 mice were treated with GalNAc-HBV-siRNA to lower HBsAg levels and then vaccinated using a DNA vaccine. We used single-cell RNA and V(D)J sequencing to understand liver immune microenvironment changes. Results: GalNAc-HBV-siRNA, followed by therapeutic vaccination, achieved sustained HBsAg loss in all mice. This was accompanied by CD4 follicular helper T-cell induction, polyclonal activation of CD8 T cells and clonal expansion of plasma cells that were responsible for antibody production. Conclusions: This study provides novel insights into liver immune changes at the single-cell level, highlighting the correlation between induced reduction of HBsAg levels and clonal expansion of CD4, CD8 T cells and plasma cells in the liver upon HBV siRNA and subsequent therapeutic vaccination. HBV single-cell-RNA sequencing liver cytotoxic CD8 T cells CD4 follicular helper T cells vaccine Medicine R Wim Pierson verfasserin aut Maurizio Vacca verfasserin aut Matthias Beyens verfasserin aut Ben De Clerck verfasserin aut Liese Aerts verfasserin aut Birgit Voeten verfasserin aut Dorien De Pooter verfasserin aut Lore Verschueren verfasserin aut Koen Dockx verfasserin aut Mathias Vandenberk verfasserin aut Ewoud De Troyer verfasserin aut Kato Verwilt verfasserin aut Carl Van Hove verfasserin aut Mieke Verslegers verfasserin aut Leslie Bosseler verfasserin aut Marjolein Crabbe verfasserin aut Vinod Krishna verfasserin aut Isabel Nájera verfasserin aut Ellen Van Gulck verfasserin aut In Vaccines MDPI AG, 2013 11(2023), 12, p 1825 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:11 year:2023 number:12, p 1825 https://doi.org/10.3390/vaccines11121825 kostenfrei https://doaj.org/article/02d6e9e3b591445ea06f0b781cc5a5c2 kostenfrei https://www.mdpi.com/2076-393X/11/12/1825 kostenfrei https://doaj.org/toc/2076-393X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2023 12, p 1825
allfieldsSound	10.3390/vaccines11121825 doi (DE-627)DOAJ098785559 (DE-599)DOAJ02d6e9e3b591445ea06f0b781cc5a5c2 DE-627 ger DE-627 rakwb eng Nádia Conceição-Neto verfasserin aut Sustained Liver HBsAg Loss and Clonal T- and B-Cell Expansion upon Therapeutic DNA Vaccination Require Low HBsAg Levels 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Suppression of HBV DNA, inhibition of HBV surface (HBsAg) production and therapeutic vaccination to reverse HBV-specific T-cell exhaustion in chronic HBV patients are likely required to achieve a functional cure. In the AAV-HBV mouse model, therapeutic vaccination can be effective in clearing HBV when HBsAg levels are low. Using a single-cell approach, we investigated the liver immune environment with different levels of HBsAg and sustained HBsAg loss through treatment with a GalNAc-HBV-siRNA followed by therapeutic vaccination. Methods: AAV-HBV-transduced C57BL/6 mice were treated with GalNAc-HBV-siRNA to lower HBsAg levels and then vaccinated using a DNA vaccine. We used single-cell RNA and V(D)J sequencing to understand liver immune microenvironment changes. Results: GalNAc-HBV-siRNA, followed by therapeutic vaccination, achieved sustained HBsAg loss in all mice. This was accompanied by CD4 follicular helper T-cell induction, polyclonal activation of CD8 T cells and clonal expansion of plasma cells that were responsible for antibody production. Conclusions: This study provides novel insights into liver immune changes at the single-cell level, highlighting the correlation between induced reduction of HBsAg levels and clonal expansion of CD4, CD8 T cells and plasma cells in the liver upon HBV siRNA and subsequent therapeutic vaccination. HBV single-cell-RNA sequencing liver cytotoxic CD8 T cells CD4 follicular helper T cells vaccine Medicine R Wim Pierson verfasserin aut Maurizio Vacca verfasserin aut Matthias Beyens verfasserin aut Ben De Clerck verfasserin aut Liese Aerts verfasserin aut Birgit Voeten verfasserin aut Dorien De Pooter verfasserin aut Lore Verschueren verfasserin aut Koen Dockx verfasserin aut Mathias Vandenberk verfasserin aut Ewoud De Troyer verfasserin aut Kato Verwilt verfasserin aut Carl Van Hove verfasserin aut Mieke Verslegers verfasserin aut Leslie Bosseler verfasserin aut Marjolein Crabbe verfasserin aut Vinod Krishna verfasserin aut Isabel Nájera verfasserin aut Ellen Van Gulck verfasserin aut In Vaccines MDPI AG, 2013 11(2023), 12, p 1825 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:11 year:2023 number:12, p 1825 https://doi.org/10.3390/vaccines11121825 kostenfrei https://doaj.org/article/02d6e9e3b591445ea06f0b781cc5a5c2 kostenfrei https://www.mdpi.com/2076-393X/11/12/1825 kostenfrei https://doaj.org/toc/2076-393X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2023 12, p 1825
language	English
source	In Vaccines 11(2023), 12, p 1825 volume:11 year:2023 number:12, p 1825
sourceStr	In Vaccines 11(2023), 12, p 1825 volume:11 year:2023 number:12, p 1825
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	HBV single-cell-RNA sequencing liver cytotoxic CD8 T cells CD4 follicular helper T cells vaccine Medicine R
isfreeaccess_bool	true
container_title	Vaccines
authorswithroles_txt_mv	Nádia Conceição-Neto @@aut@@ Wim Pierson @@aut@@ Maurizio Vacca @@aut@@ Matthias Beyens @@aut@@ Ben De Clerck @@aut@@ Liese Aerts @@aut@@ Birgit Voeten @@aut@@ Dorien De Pooter @@aut@@ Lore Verschueren @@aut@@ Koen Dockx @@aut@@ Mathias Vandenberk @@aut@@ Ewoud De Troyer @@aut@@ Kato Verwilt @@aut@@ Carl Van Hove @@aut@@ Mieke Verslegers @@aut@@ Leslie Bosseler @@aut@@ Marjolein Crabbe @@aut@@ Vinod Krishna @@aut@@ Isabel Nájera @@aut@@ Ellen Van Gulck @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	736559205
id	DOAJ098785559
language_de	englisch
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author	Nádia Conceição-Neto
spellingShingle	Nádia Conceição-Neto misc HBV misc single-cell-RNA sequencing misc liver misc cytotoxic CD8 T cells misc CD4 follicular helper T cells misc vaccine misc Medicine misc R Sustained Liver HBsAg Loss and Clonal T- and B-Cell Expansion upon Therapeutic DNA Vaccination Require Low HBsAg Levels
authorStr	Nádia Conceição-Neto
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topic_title	Sustained Liver HBsAg Loss and Clonal T- and B-Cell Expansion upon Therapeutic DNA Vaccination Require Low HBsAg Levels HBV single-cell-RNA sequencing liver cytotoxic CD8 T cells CD4 follicular helper T cells vaccine
topic	misc HBV misc single-cell-RNA sequencing misc liver misc cytotoxic CD8 T cells misc CD4 follicular helper T cells misc vaccine misc Medicine misc R
topic_unstemmed	misc HBV misc single-cell-RNA sequencing misc liver misc cytotoxic CD8 T cells misc CD4 follicular helper T cells misc vaccine misc Medicine misc R
topic_browse	misc HBV misc single-cell-RNA sequencing misc liver misc cytotoxic CD8 T cells misc CD4 follicular helper T cells misc vaccine misc Medicine misc R
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title	Sustained Liver HBsAg Loss and Clonal T- and B-Cell Expansion upon Therapeutic DNA Vaccination Require Low HBsAg Levels
ctrlnum	(DE-627)DOAJ098785559 (DE-599)DOAJ02d6e9e3b591445ea06f0b781cc5a5c2
title_full	Sustained Liver HBsAg Loss and Clonal T- and B-Cell Expansion upon Therapeutic DNA Vaccination Require Low HBsAg Levels
author_sort	Nádia Conceição-Neto
journal	Vaccines
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author_browse	Nádia Conceição-Neto Wim Pierson Maurizio Vacca Matthias Beyens Ben De Clerck Liese Aerts Birgit Voeten Dorien De Pooter Lore Verschueren Koen Dockx Mathias Vandenberk Ewoud De Troyer Kato Verwilt Carl Van Hove Mieke Verslegers Leslie Bosseler Marjolein Crabbe Vinod Krishna Isabel Nájera Ellen Van Gulck
container_volume	11
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author-letter	Nádia Conceição-Neto
doi_str_mv	10.3390/vaccines11121825
author2-role	verfasserin
title_sort	sustained liver hbsag loss and clonal t- and b-cell expansion upon therapeutic dna vaccination require low hbsag levels
title_auth	Sustained Liver HBsAg Loss and Clonal T- and B-Cell Expansion upon Therapeutic DNA Vaccination Require Low HBsAg Levels
abstract	Background: Suppression of HBV DNA, inhibition of HBV surface (HBsAg) production and therapeutic vaccination to reverse HBV-specific T-cell exhaustion in chronic HBV patients are likely required to achieve a functional cure. In the AAV-HBV mouse model, therapeutic vaccination can be effective in clearing HBV when HBsAg levels are low. Using a single-cell approach, we investigated the liver immune environment with different levels of HBsAg and sustained HBsAg loss through treatment with a GalNAc-HBV-siRNA followed by therapeutic vaccination. Methods: AAV-HBV-transduced C57BL/6 mice were treated with GalNAc-HBV-siRNA to lower HBsAg levels and then vaccinated using a DNA vaccine. We used single-cell RNA and V(D)J sequencing to understand liver immune microenvironment changes. Results: GalNAc-HBV-siRNA, followed by therapeutic vaccination, achieved sustained HBsAg loss in all mice. This was accompanied by CD4 follicular helper T-cell induction, polyclonal activation of CD8 T cells and clonal expansion of plasma cells that were responsible for antibody production. Conclusions: This study provides novel insights into liver immune changes at the single-cell level, highlighting the correlation between induced reduction of HBsAg levels and clonal expansion of CD4, CD8 T cells and plasma cells in the liver upon HBV siRNA and subsequent therapeutic vaccination.
abstractGer	Background: Suppression of HBV DNA, inhibition of HBV surface (HBsAg) production and therapeutic vaccination to reverse HBV-specific T-cell exhaustion in chronic HBV patients are likely required to achieve a functional cure. In the AAV-HBV mouse model, therapeutic vaccination can be effective in clearing HBV when HBsAg levels are low. Using a single-cell approach, we investigated the liver immune environment with different levels of HBsAg and sustained HBsAg loss through treatment with a GalNAc-HBV-siRNA followed by therapeutic vaccination. Methods: AAV-HBV-transduced C57BL/6 mice were treated with GalNAc-HBV-siRNA to lower HBsAg levels and then vaccinated using a DNA vaccine. We used single-cell RNA and V(D)J sequencing to understand liver immune microenvironment changes. Results: GalNAc-HBV-siRNA, followed by therapeutic vaccination, achieved sustained HBsAg loss in all mice. This was accompanied by CD4 follicular helper T-cell induction, polyclonal activation of CD8 T cells and clonal expansion of plasma cells that were responsible for antibody production. Conclusions: This study provides novel insights into liver immune changes at the single-cell level, highlighting the correlation between induced reduction of HBsAg levels and clonal expansion of CD4, CD8 T cells and plasma cells in the liver upon HBV siRNA and subsequent therapeutic vaccination.
abstract_unstemmed	Background: Suppression of HBV DNA, inhibition of HBV surface (HBsAg) production and therapeutic vaccination to reverse HBV-specific T-cell exhaustion in chronic HBV patients are likely required to achieve a functional cure. In the AAV-HBV mouse model, therapeutic vaccination can be effective in clearing HBV when HBsAg levels are low. Using a single-cell approach, we investigated the liver immune environment with different levels of HBsAg and sustained HBsAg loss through treatment with a GalNAc-HBV-siRNA followed by therapeutic vaccination. Methods: AAV-HBV-transduced C57BL/6 mice were treated with GalNAc-HBV-siRNA to lower HBsAg levels and then vaccinated using a DNA vaccine. We used single-cell RNA and V(D)J sequencing to understand liver immune microenvironment changes. Results: GalNAc-HBV-siRNA, followed by therapeutic vaccination, achieved sustained HBsAg loss in all mice. This was accompanied by CD4 follicular helper T-cell induction, polyclonal activation of CD8 T cells and clonal expansion of plasma cells that were responsible for antibody production. Conclusions: This study provides novel insights into liver immune changes at the single-cell level, highlighting the correlation between induced reduction of HBsAg levels and clonal expansion of CD4, CD8 T cells and plasma cells in the liver upon HBV siRNA and subsequent therapeutic vaccination.
collection_details	GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700
container_issue	12, p 1825
title_short	Sustained Liver HBsAg Loss and Clonal T- and B-Cell Expansion upon Therapeutic DNA Vaccination Require Low HBsAg Levels
url	https://doi.org/10.3390/vaccines11121825 https://doaj.org/article/02d6e9e3b591445ea06f0b781cc5a5c2 https://www.mdpi.com/2076-393X/11/12/1825 https://doaj.org/toc/2076-393X
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author2	Wim Pierson Maurizio Vacca Matthias Beyens Ben De Clerck Liese Aerts Birgit Voeten Dorien De Pooter Lore Verschueren Koen Dockx Mathias Vandenberk Ewoud De Troyer Kato Verwilt Carl Van Hove Mieke Verslegers Leslie Bosseler Marjolein Crabbe Vinod Krishna Isabel Nájera Ellen Van Gulck
author2Str	Wim Pierson Maurizio Vacca Matthias Beyens Ben De Clerck Liese Aerts Birgit Voeten Dorien De Pooter Lore Verschueren Koen Dockx Mathias Vandenberk Ewoud De Troyer Kato Verwilt Carl Van Hove Mieke Verslegers Leslie Bosseler Marjolein Crabbe Vinod Krishna Isabel Nájera Ellen Van Gulck
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doi_str	10.3390/vaccines11121825
up_date	2024-07-03T19:12:14.730Z
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Sustained Liver HBsAg Loss and Clonal T- and B-Cell Expansion upon Therapeutic DNA Vaccination Require Low HBsAg Levels

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