Development of surface engineered antigenic exosomes as vaccines for respiratory syncytial virus

Abstract Respiratory syncytial virus (RSV) is one of the main pathogens associated with lower respiratory tract infections in infants and young children worldwide. Exosomes secreted by antigen presenting cells (APCs) can elicit immune responses by carrying major histocompatibility complex (MHC) clas...

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Autores principales: Suyeon Hong, Shaobo Ruan, Zachary Greenberg, Mei He, Jodi L. McGill
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Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/84ecf41bbf6f4edc8615a68cd553ed8f
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spelling oai:doaj.org-article:84ecf41bbf6f4edc8615a68cd553ed8f2021-11-08T10:51:34ZDevelopment of surface engineered antigenic exosomes as vaccines for respiratory syncytial virus10.1038/s41598-021-00765-x2045-2322https://doaj.org/article/84ecf41bbf6f4edc8615a68cd553ed8f2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-00765-xhttps://doaj.org/toc/2045-2322Abstract Respiratory syncytial virus (RSV) is one of the main pathogens associated with lower respiratory tract infections in infants and young children worldwide. Exosomes secreted by antigen presenting cells (APCs) can elicit immune responses by carrying major histocompatibility complex (MHC) class I molecules complexed with antigenic peptides and other co-stimulating factors. Therefore, we developed novel immunomagnetic nanographene particles to sequentially isolate, surface engineer, and release intact dendritic cell (DC) exosomes for use as a potential vaccine platform against RSV. The H-2Db-restricted, immunodominant peptides from RSV (M187–195 and NS161–75) were introduced to MHC-I on DC-derived exosomes to express peptide/MHC-I (pMHC-I) complexes. A mouse model of RSV infection was used to define the immunogenicity of surface engineered exosomes for activating virus-specific immune responses. Ex vivo assays demonstrated that engineered exosomes carrying RSV-specific peptides can elicit interferon-gamma (IFN-γ) production by virus-specific CD8+ T cells isolated from RSV-infected C57BL/6 mice. In vivo assays demonstrated that subcutaneous administration of both M187–195 and NS161–75 engineered exosomes to mice, with or without additional adjuvant, appeared safe and well tolerated, however, did not prime antigen-specific CD8+ T cell responses. Surface engineered exosomes are immunogenic and promising for further development as a vaccine platform.Suyeon HongShaobo RuanZachary GreenbergMei HeJodi L. McGillNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Suyeon Hong
Shaobo Ruan
Zachary Greenberg
Mei He
Jodi L. McGill
Development of surface engineered antigenic exosomes as vaccines for respiratory syncytial virus
description Abstract Respiratory syncytial virus (RSV) is one of the main pathogens associated with lower respiratory tract infections in infants and young children worldwide. Exosomes secreted by antigen presenting cells (APCs) can elicit immune responses by carrying major histocompatibility complex (MHC) class I molecules complexed with antigenic peptides and other co-stimulating factors. Therefore, we developed novel immunomagnetic nanographene particles to sequentially isolate, surface engineer, and release intact dendritic cell (DC) exosomes for use as a potential vaccine platform against RSV. The H-2Db-restricted, immunodominant peptides from RSV (M187–195 and NS161–75) were introduced to MHC-I on DC-derived exosomes to express peptide/MHC-I (pMHC-I) complexes. A mouse model of RSV infection was used to define the immunogenicity of surface engineered exosomes for activating virus-specific immune responses. Ex vivo assays demonstrated that engineered exosomes carrying RSV-specific peptides can elicit interferon-gamma (IFN-γ) production by virus-specific CD8+ T cells isolated from RSV-infected C57BL/6 mice. In vivo assays demonstrated that subcutaneous administration of both M187–195 and NS161–75 engineered exosomes to mice, with or without additional adjuvant, appeared safe and well tolerated, however, did not prime antigen-specific CD8+ T cell responses. Surface engineered exosomes are immunogenic and promising for further development as a vaccine platform.
format article
author Suyeon Hong
Shaobo Ruan
Zachary Greenberg
Mei He
Jodi L. McGill
author_facet Suyeon Hong
Shaobo Ruan
Zachary Greenberg
Mei He
Jodi L. McGill
author_sort Suyeon Hong
title Development of surface engineered antigenic exosomes as vaccines for respiratory syncytial virus
title_short Development of surface engineered antigenic exosomes as vaccines for respiratory syncytial virus
title_full Development of surface engineered antigenic exosomes as vaccines for respiratory syncytial virus
title_fullStr Development of surface engineered antigenic exosomes as vaccines for respiratory syncytial virus
title_full_unstemmed Development of surface engineered antigenic exosomes as vaccines for respiratory syncytial virus
title_sort development of surface engineered antigenic exosomes as vaccines for respiratory syncytial virus
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/84ecf41bbf6f4edc8615a68cd553ed8f
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AT zacharygreenberg developmentofsurfaceengineeredantigenicexosomesasvaccinesforrespiratorysyncytialvirus
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