Dendritic Cell-Specific Antigen Delivery by Coronavirus Vaccine Vectors Induces Long-Lasting Protective Antiviral and Antitumor Immunity

ABSTRACT Efficient vaccination against infectious agents and tumors depends on specific antigen targeting to dendritic cells (DCs). We report here that biosafe coronavirus-based vaccine vectors facilitate delivery of multiple antigens and immunostimulatory cytokines to professional antigen-presentin...

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Autores principales:	Luisa Cervantes-Barragan, Roland Züst, Reinhard Maier, Sophie Sierro, Jozef Janda, Frederic Levy, Daniel Speiser, Pedro Romero, Pierre-Simon Rohrlich, Burkhard Ludewig, Volker Thiel
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2010
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e25819499c9c49ca9527573fd48a887c
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spelling	oai:doaj.org-article:e25819499c9c49ca9527573fd48a887c2021-11-15T15:38:15ZDendritic Cell-Specific Antigen Delivery by Coronavirus Vaccine Vectors Induces Long-Lasting Protective Antiviral and Antitumor Immunity10.1128/mBio.00171-102150-7511https://doaj.org/article/e25819499c9c49ca9527573fd48a887c2010-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00171-10https://doaj.org/toc/2150-7511ABSTRACT Efficient vaccination against infectious agents and tumors depends on specific antigen targeting to dendritic cells (DCs). We report here that biosafe coronavirus-based vaccine vectors facilitate delivery of multiple antigens and immunostimulatory cytokines to professional antigen-presenting cells in vitro and in vivo. Vaccine vectors based on heavily attenuated murine coronavirus genomes were generated to express epitopes from the lymphocytic choriomeningitis virus glycoprotein, or human Melan-A, in combination with the immunostimulatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). These vectors selectively targeted DCs in vitro and in vivo resulting in vector-mediated antigen expression and efficient maturation of DCs. Single application of only low vector doses elicited strong and long-lasting cytotoxic T-cell responses, providing protective antiviral and antitumor immunity. Furthermore, human DCs transduced with Melan-A-recombinant human coronavirus 229E efficiently activated tumor-specific CD8+ T cells. Taken together, this novel vaccine platform is well suited to deliver antigens and immunostimulatory cytokines to DCs and to initiate and maintain protective immunity. IMPORTANCE Vaccination against infectious agents has protected many individuals from severe disease. In addition, prophylactic and, most likely, also therapeutic vaccination against tumors will save millions from metastatic disease. This study describes a novel vaccine approach that facilitates delivery of viral or tumor antigens to dendritic cells in vivo. Concomitant immunostimulation via the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) was achieved through delivery by the same viral vector. Single immunization with only low doses of coronavirus-based vaccine vectors was sufficient to elicit (i) vigorous expansion and optimal differentiation of CD8+ T cells, (ii) protective and long-lasting antiviral immunity, and (iii) prophylactic and therapeutic tumor immunity. Moreover, highly efficient antigen delivery to human DCs with recombinant human coronavirus 229E and specific stimulation of human CD8+ T cells revealed that this approach is exceptionally well suited for translation into human vaccine studies.Luisa Cervantes-BarraganRoland ZüstReinhard MaierSophie SierroJozef JandaFrederic LevyDaniel SpeiserPedro RomeroPierre-Simon RohrlichBurkhard LudewigVolker ThielAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 1, Iss 4 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Luisa Cervantes-Barragan Roland Züst Reinhard Maier Sophie Sierro Jozef Janda Frederic Levy Daniel Speiser Pedro Romero Pierre-Simon Rohrlich Burkhard Ludewig Volker Thiel Dendritic Cell-Specific Antigen Delivery by Coronavirus Vaccine Vectors Induces Long-Lasting Protective Antiviral and Antitumor Immunity
description	ABSTRACT Efficient vaccination against infectious agents and tumors depends on specific antigen targeting to dendritic cells (DCs). We report here that biosafe coronavirus-based vaccine vectors facilitate delivery of multiple antigens and immunostimulatory cytokines to professional antigen-presenting cells in vitro and in vivo. Vaccine vectors based on heavily attenuated murine coronavirus genomes were generated to express epitopes from the lymphocytic choriomeningitis virus glycoprotein, or human Melan-A, in combination with the immunostimulatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). These vectors selectively targeted DCs in vitro and in vivo resulting in vector-mediated antigen expression and efficient maturation of DCs. Single application of only low vector doses elicited strong and long-lasting cytotoxic T-cell responses, providing protective antiviral and antitumor immunity. Furthermore, human DCs transduced with Melan-A-recombinant human coronavirus 229E efficiently activated tumor-specific CD8+ T cells. Taken together, this novel vaccine platform is well suited to deliver antigens and immunostimulatory cytokines to DCs and to initiate and maintain protective immunity. IMPORTANCE Vaccination against infectious agents has protected many individuals from severe disease. In addition, prophylactic and, most likely, also therapeutic vaccination against tumors will save millions from metastatic disease. This study describes a novel vaccine approach that facilitates delivery of viral or tumor antigens to dendritic cells in vivo. Concomitant immunostimulation via the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) was achieved through delivery by the same viral vector. Single immunization with only low doses of coronavirus-based vaccine vectors was sufficient to elicit (i) vigorous expansion and optimal differentiation of CD8+ T cells, (ii) protective and long-lasting antiviral immunity, and (iii) prophylactic and therapeutic tumor immunity. Moreover, highly efficient antigen delivery to human DCs with recombinant human coronavirus 229E and specific stimulation of human CD8+ T cells revealed that this approach is exceptionally well suited for translation into human vaccine studies.
format	article
author	Luisa Cervantes-Barragan Roland Züst Reinhard Maier Sophie Sierro Jozef Janda Frederic Levy Daniel Speiser Pedro Romero Pierre-Simon Rohrlich Burkhard Ludewig Volker Thiel
author_facet	Luisa Cervantes-Barragan Roland Züst Reinhard Maier Sophie Sierro Jozef Janda Frederic Levy Daniel Speiser Pedro Romero Pierre-Simon Rohrlich Burkhard Ludewig Volker Thiel
author_sort	Luisa Cervantes-Barragan
title	Dendritic Cell-Specific Antigen Delivery by Coronavirus Vaccine Vectors Induces Long-Lasting Protective Antiviral and Antitumor Immunity
title_short	Dendritic Cell-Specific Antigen Delivery by Coronavirus Vaccine Vectors Induces Long-Lasting Protective Antiviral and Antitumor Immunity
title_full	Dendritic Cell-Specific Antigen Delivery by Coronavirus Vaccine Vectors Induces Long-Lasting Protective Antiviral and Antitumor Immunity
title_fullStr	Dendritic Cell-Specific Antigen Delivery by Coronavirus Vaccine Vectors Induces Long-Lasting Protective Antiviral and Antitumor Immunity
title_full_unstemmed	Dendritic Cell-Specific Antigen Delivery by Coronavirus Vaccine Vectors Induces Long-Lasting Protective Antiviral and Antitumor Immunity
title_sort	dendritic cell-specific antigen delivery by coronavirus vaccine vectors induces long-lasting protective antiviral and antitumor immunity
publisher	American Society for Microbiology
publishDate	2010
url	https://doaj.org/article/e25819499c9c49ca9527573fd48a887c
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Dendritic Cell-Specific Antigen Delivery by Coronavirus Vaccine Vectors Induces Long-Lasting Protective Antiviral and Antitumor Immunity

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