An Intranasal Vaccine Based on Outer Membrane Vesicles Against SARS-CoV-2

The prevailing pandemic of SARS-CoV-2 highlights the desperate need of alternative vaccine-platforms, which are safe, effective, and can be modified to carry antigens of emerging pathogens. The current SARS-CoV-2 vaccines based on mRNA and adenoviral vector technology meet some of these criteria but...

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Autores principales:	Himadri B. Thapa, Anna M. Müller, Andrew Camilli, Stefan Schild
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	outer membrane vesicles Spike protein SARS-CoV-2 RBD Vibrio cholerae enterotoxigenic Escherichia coli Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/f3db165878514641bd9bcc7d26aa6cf4
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id	oai:doaj.org-article:f3db165878514641bd9bcc7d26aa6cf4
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spelling	oai:doaj.org-article:f3db165878514641bd9bcc7d26aa6cf42021-11-05T14:31:48ZAn Intranasal Vaccine Based on Outer Membrane Vesicles Against SARS-CoV-21664-302X10.3389/fmicb.2021.752739https://doaj.org/article/f3db165878514641bd9bcc7d26aa6cf42021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.752739/fullhttps://doaj.org/toc/1664-302XThe prevailing pandemic of SARS-CoV-2 highlights the desperate need of alternative vaccine-platforms, which are safe, effective, and can be modified to carry antigens of emerging pathogens. The current SARS-CoV-2 vaccines based on mRNA and adenoviral vector technology meet some of these criteria but still face limitations regarding administration route, mass production, stability, and storage. Herein, we introduce a novel SARS-CoV-2 vaccine candidate based on bacterial outer membrane vesicles (OMVs). Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC) have been genetically modified to produce increased amounts of detoxified OMVs decorated with the receptor binding domain (RBD) of the SARS-CoV-2 Spike protein. Intranasal immunization with RBD-decorated OMVs induced not only a robust immune response against the bacterial outer membrane components but also detectable antibody titers against the Spike protein. Cell culture infection assays using a Spike-pseudotyped lentivirus confirmed the presence of SARS-CoV-2 neutralizing antibodies. Highest titers against the SARS-CoV-2 Spike protein and most potent neutralization activity were observed for an alternating immunization regimen using RBD-decorated OMVs from ETEC and V. cholerae in turn. These results highlight the versatile vaccine applications offered by OMVs via expression of heterologous antigens in the donor bacterium.Himadri B. ThapaAnna M. MüllerAndrew CamilliStefan SchildStefan SchildStefan SchildFrontiers Media S.A.articleouter membrane vesiclesSpike proteinSARS-CoV-2RBDVibrio choleraeenterotoxigenic Escherichia coliMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	outer membrane vesicles Spike protein SARS-CoV-2 RBD Vibrio cholerae enterotoxigenic Escherichia coli Microbiology QR1-502
spellingShingle	outer membrane vesicles Spike protein SARS-CoV-2 RBD Vibrio cholerae enterotoxigenic Escherichia coli Microbiology QR1-502 Himadri B. Thapa Anna M. Müller Andrew Camilli Stefan Schild Stefan Schild Stefan Schild An Intranasal Vaccine Based on Outer Membrane Vesicles Against SARS-CoV-2
description	The prevailing pandemic of SARS-CoV-2 highlights the desperate need of alternative vaccine-platforms, which are safe, effective, and can be modified to carry antigens of emerging pathogens. The current SARS-CoV-2 vaccines based on mRNA and adenoviral vector technology meet some of these criteria but still face limitations regarding administration route, mass production, stability, and storage. Herein, we introduce a novel SARS-CoV-2 vaccine candidate based on bacterial outer membrane vesicles (OMVs). Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC) have been genetically modified to produce increased amounts of detoxified OMVs decorated with the receptor binding domain (RBD) of the SARS-CoV-2 Spike protein. Intranasal immunization with RBD-decorated OMVs induced not only a robust immune response against the bacterial outer membrane components but also detectable antibody titers against the Spike protein. Cell culture infection assays using a Spike-pseudotyped lentivirus confirmed the presence of SARS-CoV-2 neutralizing antibodies. Highest titers against the SARS-CoV-2 Spike protein and most potent neutralization activity were observed for an alternating immunization regimen using RBD-decorated OMVs from ETEC and V. cholerae in turn. These results highlight the versatile vaccine applications offered by OMVs via expression of heterologous antigens in the donor bacterium.
format	article
author	Himadri B. Thapa Anna M. Müller Andrew Camilli Stefan Schild Stefan Schild Stefan Schild
author_facet	Himadri B. Thapa Anna M. Müller Andrew Camilli Stefan Schild Stefan Schild Stefan Schild
author_sort	Himadri B. Thapa
title	An Intranasal Vaccine Based on Outer Membrane Vesicles Against SARS-CoV-2
title_short	An Intranasal Vaccine Based on Outer Membrane Vesicles Against SARS-CoV-2
title_full	An Intranasal Vaccine Based on Outer Membrane Vesicles Against SARS-CoV-2
title_fullStr	An Intranasal Vaccine Based on Outer Membrane Vesicles Against SARS-CoV-2
title_full_unstemmed	An Intranasal Vaccine Based on Outer Membrane Vesicles Against SARS-CoV-2
title_sort	intranasal vaccine based on outer membrane vesicles against sars-cov-2
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/f3db165878514641bd9bcc7d26aa6cf4
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An Intranasal Vaccine Based on Outer Membrane Vesicles Against SARS-CoV-2

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