Modulation of Vaccine-Induced HIV-1-Specific Immune Responses by Co-Electroporation of PD-L1 Encoding DNA

The importance of a balanced T<sub<H</sub<1/T<sub<H</sub<2 humoral immune response against the HIV-1 envelope protein (Env) for antibody-mediated HIV-1 control is increasingly recognized. However, there is no defined vaccination strategy to raise it. Since immune checkpoints...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Pierre Tannig [verfasserIn] Antonia Sophia Peter [verfasserIn] Dennis Lapuente [verfasserIn] Stephan Klessing [verfasserIn] Dominik Damm [verfasserIn] Matthias Tenbusch [verfasserIn] Klaus Überla [verfasserIn] Vladimir Temchura [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	hiv-1 checkpoint inhibitors checkpoint blockade intramuscular electroporation soluble immune checkpoints immunomodulation

Übergeordnetes Werk:	In: Vaccines - MDPI AG, 2013, 8(2020), 1, p 27
Übergeordnetes Werk:	volume:8 ; year:2020 ; number:1, p 27

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/vaccines8010027

Katalog-ID:	DOAJ02585643X

Internformat


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allfields	10.3390/vaccines8010027 doi (DE-627)DOAJ02585643X (DE-599)DOAJb11748c22f39473c8006a055ee75f532 DE-627 ger DE-627 rakwb eng Pierre Tannig verfasserin aut Modulation of Vaccine-Induced HIV-1-Specific Immune Responses by Co-Electroporation of PD-L1 Encoding DNA 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The importance of a balanced T<sub<H</sub<1/T<sub<H</sub<2 humoral immune response against the HIV-1 envelope protein (Env) for antibody-mediated HIV-1 control is increasingly recognized. However, there is no defined vaccination strategy to raise it. Since immune checkpoints are involved in the induction of adoptive immunity and their inhibitors (monoclonal antibodies) are licensed for cancer therapy, we investigated the effect of checkpoint blockade after HIV-1 genetic vaccination on enhancement and modulation of antiviral antibody responses. By intraperitoneal administration of checkpoint antibodies in mice we observed an induction of anti-drug antibodies which may interfere with immunomodulation by checkpoint inhibitors. Therefore, we blocked immune checkpoints locally by co-electroporation of DNA vaccines encoding the active soluble ectodomains of programmed cell death protein-1 (PD-1) or its ligand (PD-L1), respectively. Plasmid-encoded immune checkpoints did not elicit a detectable antibody response, suggesting no interference with their immunomodulatory effects. Co-electroporation of a HIV-1 DNA vaccine formulation with soluble PD-L1 ectodomain increased HIV-1 Env-specific T<sub<H</sub<1 CD4 T cell and IgG2a antibody responses. The overall antibody response was hereby shifted towards a more T<sub<H</sub<1/T<sub<H</sub<2 balanced subtype pattern. These findings indicate that co-electroporation of soluble checkpoint ectodomains together with DNA-based vaccines has modulatory effects on vaccine-induced immune responses that could improve vaccine efficacies. hiv-1 checkpoint inhibitors checkpoint blockade intramuscular electroporation soluble immune checkpoints immunomodulation Medicine R Antonia Sophia Peter verfasserin aut Dennis Lapuente verfasserin aut Stephan Klessing verfasserin aut Dominik Damm verfasserin aut Matthias Tenbusch verfasserin aut Klaus Überla verfasserin aut Vladimir Temchura verfasserin aut In Vaccines MDPI AG, 2013 8(2020), 1, p 27 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:8 year:2020 number:1, p 27 https://doi.org/10.3390/vaccines8010027 kostenfrei https://doaj.org/article/b11748c22f39473c8006a055ee75f532 kostenfrei https://www.mdpi.com/2076-393X/8/1/27 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 8 2020 1, p 27
spelling	10.3390/vaccines8010027 doi (DE-627)DOAJ02585643X (DE-599)DOAJb11748c22f39473c8006a055ee75f532 DE-627 ger DE-627 rakwb eng Pierre Tannig verfasserin aut Modulation of Vaccine-Induced HIV-1-Specific Immune Responses by Co-Electroporation of PD-L1 Encoding DNA 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The importance of a balanced T<sub<H</sub<1/T<sub<H</sub<2 humoral immune response against the HIV-1 envelope protein (Env) for antibody-mediated HIV-1 control is increasingly recognized. However, there is no defined vaccination strategy to raise it. Since immune checkpoints are involved in the induction of adoptive immunity and their inhibitors (monoclonal antibodies) are licensed for cancer therapy, we investigated the effect of checkpoint blockade after HIV-1 genetic vaccination on enhancement and modulation of antiviral antibody responses. By intraperitoneal administration of checkpoint antibodies in mice we observed an induction of anti-drug antibodies which may interfere with immunomodulation by checkpoint inhibitors. Therefore, we blocked immune checkpoints locally by co-electroporation of DNA vaccines encoding the active soluble ectodomains of programmed cell death protein-1 (PD-1) or its ligand (PD-L1), respectively. Plasmid-encoded immune checkpoints did not elicit a detectable antibody response, suggesting no interference with their immunomodulatory effects. Co-electroporation of a HIV-1 DNA vaccine formulation with soluble PD-L1 ectodomain increased HIV-1 Env-specific T<sub<H</sub<1 CD4 T cell and IgG2a antibody responses. The overall antibody response was hereby shifted towards a more T<sub<H</sub<1/T<sub<H</sub<2 balanced subtype pattern. These findings indicate that co-electroporation of soluble checkpoint ectodomains together with DNA-based vaccines has modulatory effects on vaccine-induced immune responses that could improve vaccine efficacies. hiv-1 checkpoint inhibitors checkpoint blockade intramuscular electroporation soluble immune checkpoints immunomodulation Medicine R Antonia Sophia Peter verfasserin aut Dennis Lapuente verfasserin aut Stephan Klessing verfasserin aut Dominik Damm verfasserin aut Matthias Tenbusch verfasserin aut Klaus Überla verfasserin aut Vladimir Temchura verfasserin aut In Vaccines MDPI AG, 2013 8(2020), 1, p 27 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:8 year:2020 number:1, p 27 https://doi.org/10.3390/vaccines8010027 kostenfrei https://doaj.org/article/b11748c22f39473c8006a055ee75f532 kostenfrei https://www.mdpi.com/2076-393X/8/1/27 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 8 2020 1, p 27
allfields_unstemmed	10.3390/vaccines8010027 doi (DE-627)DOAJ02585643X (DE-599)DOAJb11748c22f39473c8006a055ee75f532 DE-627 ger DE-627 rakwb eng Pierre Tannig verfasserin aut Modulation of Vaccine-Induced HIV-1-Specific Immune Responses by Co-Electroporation of PD-L1 Encoding DNA 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The importance of a balanced T<sub<H</sub<1/T<sub<H</sub<2 humoral immune response against the HIV-1 envelope protein (Env) for antibody-mediated HIV-1 control is increasingly recognized. However, there is no defined vaccination strategy to raise it. Since immune checkpoints are involved in the induction of adoptive immunity and their inhibitors (monoclonal antibodies) are licensed for cancer therapy, we investigated the effect of checkpoint blockade after HIV-1 genetic vaccination on enhancement and modulation of antiviral antibody responses. By intraperitoneal administration of checkpoint antibodies in mice we observed an induction of anti-drug antibodies which may interfere with immunomodulation by checkpoint inhibitors. Therefore, we blocked immune checkpoints locally by co-electroporation of DNA vaccines encoding the active soluble ectodomains of programmed cell death protein-1 (PD-1) or its ligand (PD-L1), respectively. Plasmid-encoded immune checkpoints did not elicit a detectable antibody response, suggesting no interference with their immunomodulatory effects. Co-electroporation of a HIV-1 DNA vaccine formulation with soluble PD-L1 ectodomain increased HIV-1 Env-specific T<sub<H</sub<1 CD4 T cell and IgG2a antibody responses. The overall antibody response was hereby shifted towards a more T<sub<H</sub<1/T<sub<H</sub<2 balanced subtype pattern. These findings indicate that co-electroporation of soluble checkpoint ectodomains together with DNA-based vaccines has modulatory effects on vaccine-induced immune responses that could improve vaccine efficacies. hiv-1 checkpoint inhibitors checkpoint blockade intramuscular electroporation soluble immune checkpoints immunomodulation Medicine R Antonia Sophia Peter verfasserin aut Dennis Lapuente verfasserin aut Stephan Klessing verfasserin aut Dominik Damm verfasserin aut Matthias Tenbusch verfasserin aut Klaus Überla verfasserin aut Vladimir Temchura verfasserin aut In Vaccines MDPI AG, 2013 8(2020), 1, p 27 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:8 year:2020 number:1, p 27 https://doi.org/10.3390/vaccines8010027 kostenfrei https://doaj.org/article/b11748c22f39473c8006a055ee75f532 kostenfrei https://www.mdpi.com/2076-393X/8/1/27 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 8 2020 1, p 27
allfieldsGer	10.3390/vaccines8010027 doi (DE-627)DOAJ02585643X (DE-599)DOAJb11748c22f39473c8006a055ee75f532 DE-627 ger DE-627 rakwb eng Pierre Tannig verfasserin aut Modulation of Vaccine-Induced HIV-1-Specific Immune Responses by Co-Electroporation of PD-L1 Encoding DNA 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The importance of a balanced T<sub<H</sub<1/T<sub<H</sub<2 humoral immune response against the HIV-1 envelope protein (Env) for antibody-mediated HIV-1 control is increasingly recognized. However, there is no defined vaccination strategy to raise it. Since immune checkpoints are involved in the induction of adoptive immunity and their inhibitors (monoclonal antibodies) are licensed for cancer therapy, we investigated the effect of checkpoint blockade after HIV-1 genetic vaccination on enhancement and modulation of antiviral antibody responses. By intraperitoneal administration of checkpoint antibodies in mice we observed an induction of anti-drug antibodies which may interfere with immunomodulation by checkpoint inhibitors. Therefore, we blocked immune checkpoints locally by co-electroporation of DNA vaccines encoding the active soluble ectodomains of programmed cell death protein-1 (PD-1) or its ligand (PD-L1), respectively. Plasmid-encoded immune checkpoints did not elicit a detectable antibody response, suggesting no interference with their immunomodulatory effects. Co-electroporation of a HIV-1 DNA vaccine formulation with soluble PD-L1 ectodomain increased HIV-1 Env-specific T<sub<H</sub<1 CD4 T cell and IgG2a antibody responses. The overall antibody response was hereby shifted towards a more T<sub<H</sub<1/T<sub<H</sub<2 balanced subtype pattern. These findings indicate that co-electroporation of soluble checkpoint ectodomains together with DNA-based vaccines has modulatory effects on vaccine-induced immune responses that could improve vaccine efficacies. hiv-1 checkpoint inhibitors checkpoint blockade intramuscular electroporation soluble immune checkpoints immunomodulation Medicine R Antonia Sophia Peter verfasserin aut Dennis Lapuente verfasserin aut Stephan Klessing verfasserin aut Dominik Damm verfasserin aut Matthias Tenbusch verfasserin aut Klaus Überla verfasserin aut Vladimir Temchura verfasserin aut In Vaccines MDPI AG, 2013 8(2020), 1, p 27 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:8 year:2020 number:1, p 27 https://doi.org/10.3390/vaccines8010027 kostenfrei https://doaj.org/article/b11748c22f39473c8006a055ee75f532 kostenfrei https://www.mdpi.com/2076-393X/8/1/27 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 8 2020 1, p 27
allfieldsSound	10.3390/vaccines8010027 doi (DE-627)DOAJ02585643X (DE-599)DOAJb11748c22f39473c8006a055ee75f532 DE-627 ger DE-627 rakwb eng Pierre Tannig verfasserin aut Modulation of Vaccine-Induced HIV-1-Specific Immune Responses by Co-Electroporation of PD-L1 Encoding DNA 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The importance of a balanced T<sub<H</sub<1/T<sub<H</sub<2 humoral immune response against the HIV-1 envelope protein (Env) for antibody-mediated HIV-1 control is increasingly recognized. However, there is no defined vaccination strategy to raise it. Since immune checkpoints are involved in the induction of adoptive immunity and their inhibitors (monoclonal antibodies) are licensed for cancer therapy, we investigated the effect of checkpoint blockade after HIV-1 genetic vaccination on enhancement and modulation of antiviral antibody responses. By intraperitoneal administration of checkpoint antibodies in mice we observed an induction of anti-drug antibodies which may interfere with immunomodulation by checkpoint inhibitors. Therefore, we blocked immune checkpoints locally by co-electroporation of DNA vaccines encoding the active soluble ectodomains of programmed cell death protein-1 (PD-1) or its ligand (PD-L1), respectively. Plasmid-encoded immune checkpoints did not elicit a detectable antibody response, suggesting no interference with their immunomodulatory effects. Co-electroporation of a HIV-1 DNA vaccine formulation with soluble PD-L1 ectodomain increased HIV-1 Env-specific T<sub<H</sub<1 CD4 T cell and IgG2a antibody responses. The overall antibody response was hereby shifted towards a more T<sub<H</sub<1/T<sub<H</sub<2 balanced subtype pattern. These findings indicate that co-electroporation of soluble checkpoint ectodomains together with DNA-based vaccines has modulatory effects on vaccine-induced immune responses that could improve vaccine efficacies. hiv-1 checkpoint inhibitors checkpoint blockade intramuscular electroporation soluble immune checkpoints immunomodulation Medicine R Antonia Sophia Peter verfasserin aut Dennis Lapuente verfasserin aut Stephan Klessing verfasserin aut Dominik Damm verfasserin aut Matthias Tenbusch verfasserin aut Klaus Überla verfasserin aut Vladimir Temchura verfasserin aut In Vaccines MDPI AG, 2013 8(2020), 1, p 27 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:8 year:2020 number:1, p 27 https://doi.org/10.3390/vaccines8010027 kostenfrei https://doaj.org/article/b11748c22f39473c8006a055ee75f532 kostenfrei https://www.mdpi.com/2076-393X/8/1/27 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 8 2020 1, p 27
language	English
source	In Vaccines 8(2020), 1, p 27 volume:8 year:2020 number:1, p 27
sourceStr	In Vaccines 8(2020), 1, p 27 volume:8 year:2020 number:1, p 27
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institution	findex.gbv.de
topic_facet	hiv-1 checkpoint inhibitors checkpoint blockade intramuscular electroporation soluble immune checkpoints immunomodulation Medicine R
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container_title	Vaccines
authorswithroles_txt_mv	Pierre Tannig @@aut@@ Antonia Sophia Peter @@aut@@ Dennis Lapuente @@aut@@ Stephan Klessing @@aut@@ Dominik Damm @@aut@@ Matthias Tenbusch @@aut@@ Klaus Überla @@aut@@ Vladimir Temchura @@aut@@
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author	Pierre Tannig
spellingShingle	Pierre Tannig misc hiv-1 misc checkpoint inhibitors misc checkpoint blockade misc intramuscular electroporation misc soluble immune checkpoints misc immunomodulation misc Medicine misc R Modulation of Vaccine-Induced HIV-1-Specific Immune Responses by Co-Electroporation of PD-L1 Encoding DNA
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topic_title	Modulation of Vaccine-Induced HIV-1-Specific Immune Responses by Co-Electroporation of PD-L1 Encoding DNA hiv-1 checkpoint inhibitors checkpoint blockade intramuscular electroporation soluble immune checkpoints immunomodulation
topic	misc hiv-1 misc checkpoint inhibitors misc checkpoint blockade misc intramuscular electroporation misc soluble immune checkpoints misc immunomodulation misc Medicine misc R
topic_unstemmed	misc hiv-1 misc checkpoint inhibitors misc checkpoint blockade misc intramuscular electroporation misc soluble immune checkpoints misc immunomodulation misc Medicine misc R
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title	Modulation of Vaccine-Induced HIV-1-Specific Immune Responses by Co-Electroporation of PD-L1 Encoding DNA
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title_full	Modulation of Vaccine-Induced HIV-1-Specific Immune Responses by Co-Electroporation of PD-L1 Encoding DNA
author_sort	Pierre Tannig
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author_browse	Pierre Tannig Antonia Sophia Peter Dennis Lapuente Stephan Klessing Dominik Damm Matthias Tenbusch Klaus Überla Vladimir Temchura
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title_sort	modulation of vaccine-induced hiv-1-specific immune responses by co-electroporation of pd-l1 encoding dna
title_auth	Modulation of Vaccine-Induced HIV-1-Specific Immune Responses by Co-Electroporation of PD-L1 Encoding DNA
abstract	The importance of a balanced T<sub<H</sub<1/T<sub<H</sub<2 humoral immune response against the HIV-1 envelope protein (Env) for antibody-mediated HIV-1 control is increasingly recognized. However, there is no defined vaccination strategy to raise it. Since immune checkpoints are involved in the induction of adoptive immunity and their inhibitors (monoclonal antibodies) are licensed for cancer therapy, we investigated the effect of checkpoint blockade after HIV-1 genetic vaccination on enhancement and modulation of antiviral antibody responses. By intraperitoneal administration of checkpoint antibodies in mice we observed an induction of anti-drug antibodies which may interfere with immunomodulation by checkpoint inhibitors. Therefore, we blocked immune checkpoints locally by co-electroporation of DNA vaccines encoding the active soluble ectodomains of programmed cell death protein-1 (PD-1) or its ligand (PD-L1), respectively. Plasmid-encoded immune checkpoints did not elicit a detectable antibody response, suggesting no interference with their immunomodulatory effects. Co-electroporation of a HIV-1 DNA vaccine formulation with soluble PD-L1 ectodomain increased HIV-1 Env-specific T<sub<H</sub<1 CD4 T cell and IgG2a antibody responses. The overall antibody response was hereby shifted towards a more T<sub<H</sub<1/T<sub<H</sub<2 balanced subtype pattern. These findings indicate that co-electroporation of soluble checkpoint ectodomains together with DNA-based vaccines has modulatory effects on vaccine-induced immune responses that could improve vaccine efficacies.
abstractGer	The importance of a balanced T<sub<H</sub<1/T<sub<H</sub<2 humoral immune response against the HIV-1 envelope protein (Env) for antibody-mediated HIV-1 control is increasingly recognized. However, there is no defined vaccination strategy to raise it. Since immune checkpoints are involved in the induction of adoptive immunity and their inhibitors (monoclonal antibodies) are licensed for cancer therapy, we investigated the effect of checkpoint blockade after HIV-1 genetic vaccination on enhancement and modulation of antiviral antibody responses. By intraperitoneal administration of checkpoint antibodies in mice we observed an induction of anti-drug antibodies which may interfere with immunomodulation by checkpoint inhibitors. Therefore, we blocked immune checkpoints locally by co-electroporation of DNA vaccines encoding the active soluble ectodomains of programmed cell death protein-1 (PD-1) or its ligand (PD-L1), respectively. Plasmid-encoded immune checkpoints did not elicit a detectable antibody response, suggesting no interference with their immunomodulatory effects. Co-electroporation of a HIV-1 DNA vaccine formulation with soluble PD-L1 ectodomain increased HIV-1 Env-specific T<sub<H</sub<1 CD4 T cell and IgG2a antibody responses. The overall antibody response was hereby shifted towards a more T<sub<H</sub<1/T<sub<H</sub<2 balanced subtype pattern. These findings indicate that co-electroporation of soluble checkpoint ectodomains together with DNA-based vaccines has modulatory effects on vaccine-induced immune responses that could improve vaccine efficacies.
abstract_unstemmed	The importance of a balanced T<sub<H</sub<1/T<sub<H</sub<2 humoral immune response against the HIV-1 envelope protein (Env) for antibody-mediated HIV-1 control is increasingly recognized. However, there is no defined vaccination strategy to raise it. Since immune checkpoints are involved in the induction of adoptive immunity and their inhibitors (monoclonal antibodies) are licensed for cancer therapy, we investigated the effect of checkpoint blockade after HIV-1 genetic vaccination on enhancement and modulation of antiviral antibody responses. By intraperitoneal administration of checkpoint antibodies in mice we observed an induction of anti-drug antibodies which may interfere with immunomodulation by checkpoint inhibitors. Therefore, we blocked immune checkpoints locally by co-electroporation of DNA vaccines encoding the active soluble ectodomains of programmed cell death protein-1 (PD-1) or its ligand (PD-L1), respectively. Plasmid-encoded immune checkpoints did not elicit a detectable antibody response, suggesting no interference with their immunomodulatory effects. Co-electroporation of a HIV-1 DNA vaccine formulation with soluble PD-L1 ectodomain increased HIV-1 Env-specific T<sub<H</sub<1 CD4 T cell and IgG2a antibody responses. The overall antibody response was hereby shifted towards a more T<sub<H</sub<1/T<sub<H</sub<2 balanced subtype pattern. These findings indicate that co-electroporation of soluble checkpoint ectodomains together with DNA-based vaccines has modulatory effects on vaccine-induced immune responses that could improve vaccine efficacies.
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title_short	Modulation of Vaccine-Induced HIV-1-Specific Immune Responses by Co-Electroporation of PD-L1 Encoding DNA
url	https://doi.org/10.3390/vaccines8010027 https://doaj.org/article/b11748c22f39473c8006a055ee75f532 https://www.mdpi.com/2076-393X/8/1/27 https://doaj.org/toc/2076-393X
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author2	Antonia Sophia Peter Dennis Lapuente Stephan Klessing Dominik Damm Matthias Tenbusch Klaus Überla Vladimir Temchura
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up_date	2024-07-03T17:33:50.186Z
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Modulation of Vaccine-Induced HIV-1-Specific Immune Responses by Co-Electroporation of PD-L1 Encoding DNA

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