Virus-based vaccine vectors with distinct replication mechanisms differentially infect and activate dendritic cells

Abstract The precise mechanism by which many virus-based vectors activate immune responses remains unknown. Dendritic cells (DCs) play key roles in priming T cell responses and controlling virus replication, but their functions in generating protective immunity following vaccination with viral vecto...

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Autores principales:	Carolina Chiale, Anthony M. Marchese, Yoichi Furuya, Michael D. Robek
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/9f635bc15de044ad91eccd5d62ec3467
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spelling	oai:doaj.org-article:9f635bc15de044ad91eccd5d62ec34672021-11-28T12:06:07ZVirus-based vaccine vectors with distinct replication mechanisms differentially infect and activate dendritic cells10.1038/s41541-021-00400-w2059-0105https://doaj.org/article/9f635bc15de044ad91eccd5d62ec34672021-11-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00400-whttps://doaj.org/toc/2059-0105Abstract The precise mechanism by which many virus-based vectors activate immune responses remains unknown. Dendritic cells (DCs) play key roles in priming T cell responses and controlling virus replication, but their functions in generating protective immunity following vaccination with viral vectors are not always well understood. We hypothesized that highly immunogenic viral vectors with identical cell entry pathways but unique replication mechanisms differentially infect and activate DCs to promote antigen presentation and activation of distinctive antigen-specific T cell responses. To evaluate differences in replication mechanisms, we utilized a rhabdovirus vector (vesicular stomatitis virus; VSV) and an alphavirus-rhabdovirus hybrid vector (virus-like vesicles; VLV), which replicates like an alphavirus but enters the cell via the VSV glycoprotein. We found that while virus replication promotes CD8+ T cell activation by VLV, replication is absolutely required for VSV-induced responses. DC subtypes were differentially infected in vitro with VSV and VLV, and displayed differences in activation following infection that were dependent on vector replication but were independent of interferon receptor signaling. Additionally, the ability of the alphavirus-based vector to generate functional CD8+ T cells in the absence of replication relied on cDC1 cells. These results highlight the differential activation of DCs following infection with unique viral vectors and indicate potentially discrete roles of DC subtypes in activating the immune response following immunization with vectors that have distinct replication mechanisms.Carolina ChialeAnthony M. MarcheseYoichi FuruyaMichael D. RobekNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Carolina Chiale Anthony M. Marchese Yoichi Furuya Michael D. Robek Virus-based vaccine vectors with distinct replication mechanisms differentially infect and activate dendritic cells
description	Abstract The precise mechanism by which many virus-based vectors activate immune responses remains unknown. Dendritic cells (DCs) play key roles in priming T cell responses and controlling virus replication, but their functions in generating protective immunity following vaccination with viral vectors are not always well understood. We hypothesized that highly immunogenic viral vectors with identical cell entry pathways but unique replication mechanisms differentially infect and activate DCs to promote antigen presentation and activation of distinctive antigen-specific T cell responses. To evaluate differences in replication mechanisms, we utilized a rhabdovirus vector (vesicular stomatitis virus; VSV) and an alphavirus-rhabdovirus hybrid vector (virus-like vesicles; VLV), which replicates like an alphavirus but enters the cell via the VSV glycoprotein. We found that while virus replication promotes CD8+ T cell activation by VLV, replication is absolutely required for VSV-induced responses. DC subtypes were differentially infected in vitro with VSV and VLV, and displayed differences in activation following infection that were dependent on vector replication but were independent of interferon receptor signaling. Additionally, the ability of the alphavirus-based vector to generate functional CD8+ T cells in the absence of replication relied on cDC1 cells. These results highlight the differential activation of DCs following infection with unique viral vectors and indicate potentially discrete roles of DC subtypes in activating the immune response following immunization with vectors that have distinct replication mechanisms.
format	article
author	Carolina Chiale Anthony M. Marchese Yoichi Furuya Michael D. Robek
author_facet	Carolina Chiale Anthony M. Marchese Yoichi Furuya Michael D. Robek
author_sort	Carolina Chiale
title	Virus-based vaccine vectors with distinct replication mechanisms differentially infect and activate dendritic cells
title_short	Virus-based vaccine vectors with distinct replication mechanisms differentially infect and activate dendritic cells
title_full	Virus-based vaccine vectors with distinct replication mechanisms differentially infect and activate dendritic cells
title_fullStr	Virus-based vaccine vectors with distinct replication mechanisms differentially infect and activate dendritic cells
title_full_unstemmed	Virus-based vaccine vectors with distinct replication mechanisms differentially infect and activate dendritic cells
title_sort	virus-based vaccine vectors with distinct replication mechanisms differentially infect and activate dendritic cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9f635bc15de044ad91eccd5d62ec3467
work_keys_str_mv	AT carolinachiale virusbasedvaccinevectorswithdistinctreplicationmechanismsdifferentiallyinfectandactivatedendriticcells AT anthonymmarchese virusbasedvaccinevectorswithdistinctreplicationmechanismsdifferentiallyinfectandactivatedendriticcells AT yoichifuruya virusbasedvaccinevectorswithdistinctreplicationmechanismsdifferentiallyinfectandactivatedendriticcells AT michaeldrobek virusbasedvaccinevectorswithdistinctreplicationmechanismsdifferentiallyinfectandactivatedendriticcells
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Virus-based vaccine vectors with distinct replication mechanisms differentially infect and activate dendritic cells

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