Intranasal plus subcutaneous prime vaccination with a dual antigen COVID-19 vaccine elicits T-cell and antibody responses in mice

Abstract We have developed a COVID-19 vaccine, hAd5 S-Fusion + N-ETSD, that expresses SARS-CoV-2 spike (S) and nucleocapsid (N) proteins with modifications to increase immune responses delivered using a human adenovirus serotype 5 (hAd5) platform. Here, we demonstrate subcutaneous (SC) prime and SC...

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Autores principales:	Adrian Rice, Mohit Verma, Annie Shin, Lise Zakin, Peter Sieling, Shiho Tanaka, Joseph Balint, Kyle Dinkins, Helty Adisetiyo, Brett Morimoto, Wendy Higashide, C. Anders Olson, Shivani Mody, Patricia Spilman, Elizabeth Gabitzsch, Jeffrey T. Safrit, Shahrooz Rabizadeh, Kayvan Niazi, Patrick Soon-Shiong
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c2a806620483477893a8b28004af78a6
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spelling	oai:doaj.org-article:c2a806620483477893a8b28004af78a62021-12-02T16:26:38ZIntranasal plus subcutaneous prime vaccination with a dual antigen COVID-19 vaccine elicits T-cell and antibody responses in mice10.1038/s41598-021-94364-52045-2322https://doaj.org/article/c2a806620483477893a8b28004af78a62021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94364-5https://doaj.org/toc/2045-2322Abstract We have developed a COVID-19 vaccine, hAd5 S-Fusion + N-ETSD, that expresses SARS-CoV-2 spike (S) and nucleocapsid (N) proteins with modifications to increase immune responses delivered using a human adenovirus serotype 5 (hAd5) platform. Here, we demonstrate subcutaneous (SC) prime and SC boost vaccination of CD-1 mice with this dual-antigen vaccine elicits T-helper cell 1 (Th1) biased T-cell and humoral responses to both S and N that are greater than those seen with hAd5 S wild type delivering only unmodified S. We then compared SC to intranasal (IN) prime vaccination with SC or IN boosts and show that an IN prime with an IN boost is as effective at generating Th1 biased humoral responses as the other combinations tested, but an SC prime with an IN or SC boost elicits greater T cell responses. Finally, we used a combined SC plus IN (SC + IN) prime with or without a boost and found the SC + IN prime alone to be as effective in generating humoral and T-cell responses as the SC + IN prime with a boost. The finding that SC + IN prime-only delivery has the potential to provide broad immunity—including mucosal immunity—against SARS-CoV-2 supports further testing of this vaccine and delivery approach in animal models of viral challenge.Adrian RiceMohit VermaAnnie ShinLise ZakinPeter SielingShiho TanakaJoseph BalintKyle DinkinsHelty AdisetiyoBrett MorimotoWendy HigashideC. Anders OlsonShivani ModyPatricia SpilmanElizabeth GabitzschJeffrey T. SafritShahrooz RabizadehKayvan NiaziPatrick Soon-ShiongNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Adrian Rice Mohit Verma Annie Shin Lise Zakin Peter Sieling Shiho Tanaka Joseph Balint Kyle Dinkins Helty Adisetiyo Brett Morimoto Wendy Higashide C. Anders Olson Shivani Mody Patricia Spilman Elizabeth Gabitzsch Jeffrey T. Safrit Shahrooz Rabizadeh Kayvan Niazi Patrick Soon-Shiong Intranasal plus subcutaneous prime vaccination with a dual antigen COVID-19 vaccine elicits T-cell and antibody responses in mice
description	Abstract We have developed a COVID-19 vaccine, hAd5 S-Fusion + N-ETSD, that expresses SARS-CoV-2 spike (S) and nucleocapsid (N) proteins with modifications to increase immune responses delivered using a human adenovirus serotype 5 (hAd5) platform. Here, we demonstrate subcutaneous (SC) prime and SC boost vaccination of CD-1 mice with this dual-antigen vaccine elicits T-helper cell 1 (Th1) biased T-cell and humoral responses to both S and N that are greater than those seen with hAd5 S wild type delivering only unmodified S. We then compared SC to intranasal (IN) prime vaccination with SC or IN boosts and show that an IN prime with an IN boost is as effective at generating Th1 biased humoral responses as the other combinations tested, but an SC prime with an IN or SC boost elicits greater T cell responses. Finally, we used a combined SC plus IN (SC + IN) prime with or without a boost and found the SC + IN prime alone to be as effective in generating humoral and T-cell responses as the SC + IN prime with a boost. The finding that SC + IN prime-only delivery has the potential to provide broad immunity—including mucosal immunity—against SARS-CoV-2 supports further testing of this vaccine and delivery approach in animal models of viral challenge.
format	article
author	Adrian Rice Mohit Verma Annie Shin Lise Zakin Peter Sieling Shiho Tanaka Joseph Balint Kyle Dinkins Helty Adisetiyo Brett Morimoto Wendy Higashide C. Anders Olson Shivani Mody Patricia Spilman Elizabeth Gabitzsch Jeffrey T. Safrit Shahrooz Rabizadeh Kayvan Niazi Patrick Soon-Shiong
author_facet	Adrian Rice Mohit Verma Annie Shin Lise Zakin Peter Sieling Shiho Tanaka Joseph Balint Kyle Dinkins Helty Adisetiyo Brett Morimoto Wendy Higashide C. Anders Olson Shivani Mody Patricia Spilman Elizabeth Gabitzsch Jeffrey T. Safrit Shahrooz Rabizadeh Kayvan Niazi Patrick Soon-Shiong
author_sort	Adrian Rice
title	Intranasal plus subcutaneous prime vaccination with a dual antigen COVID-19 vaccine elicits T-cell and antibody responses in mice
title_short	Intranasal plus subcutaneous prime vaccination with a dual antigen COVID-19 vaccine elicits T-cell and antibody responses in mice
title_full	Intranasal plus subcutaneous prime vaccination with a dual antigen COVID-19 vaccine elicits T-cell and antibody responses in mice
title_fullStr	Intranasal plus subcutaneous prime vaccination with a dual antigen COVID-19 vaccine elicits T-cell and antibody responses in mice
title_full_unstemmed	Intranasal plus subcutaneous prime vaccination with a dual antigen COVID-19 vaccine elicits T-cell and antibody responses in mice
title_sort	intranasal plus subcutaneous prime vaccination with a dual antigen covid-19 vaccine elicits t-cell and antibody responses in mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c2a806620483477893a8b28004af78a6
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Intranasal plus subcutaneous prime vaccination with a dual antigen COVID-19 vaccine elicits T-cell and antibody responses in mice

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