ChAdOx1-vectored Lassa fever vaccine elicits a robust cellular and humoral immune response and protects guinea pigs against lethal Lassa virus challenge

Abstract Lassa virus (LASV) infects hundreds of thousands of individuals each year, highlighting the need for the accelerated development of preventive, diagnostic, and therapeutic interventions. To date, no vaccine has been licensed for LASV. ChAdOx1-Lassa-GPC is a chimpanzee adenovirus-vectored va...

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Autores principales:	Robert J. Fischer, Jyothi N. Purushotham, Neeltje van Doremalen, Sarah Sebastian, Kimberly Meade-White, Kathleen Cordova, Michael Letko, M. Jeremiah Matson, Friederike Feldmann, Elaine Haddock, Rachel LaCasse, Greg Saturday, Teresa Lambe, Sarah C. Gilbert, Vincent J. Munster
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/4667aaafa6c240a492ef4c7b8f637c7b
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spelling	oai:doaj.org-article:4667aaafa6c240a492ef4c7b8f637c7b2021-12-02T13:19:20ZChAdOx1-vectored Lassa fever vaccine elicits a robust cellular and humoral immune response and protects guinea pigs against lethal Lassa virus challenge10.1038/s41541-021-00291-x2059-0105https://doaj.org/article/4667aaafa6c240a492ef4c7b8f637c7b2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00291-xhttps://doaj.org/toc/2059-0105Abstract Lassa virus (LASV) infects hundreds of thousands of individuals each year, highlighting the need for the accelerated development of preventive, diagnostic, and therapeutic interventions. To date, no vaccine has been licensed for LASV. ChAdOx1-Lassa-GPC is a chimpanzee adenovirus-vectored vaccine encoding the Josiah strain LASV glycoprotein precursor (GPC) gene. In the following study, we show that ChAdOx1-Lassa-GPC is immunogenic, inducing robust T-cell and antibody responses in mice. Furthermore, a single dose of ChAdOx1-Lassa-GPC fully protects Hartley guinea pigs against morbidity and mortality following lethal challenge with a guinea pig-adapted LASV (strain Josiah). By contrast, control vaccinated animals reached euthanasia criteria 10–12 days after infection. Limited amounts of LASV RNA were detected in the tissues of vaccinated animals. Viable LASV was detected in only one animal receiving a single dose of the vaccine. A prime-boost regimen of ChAdOx1-Lassa-GPC in guinea pigs significantly increased antigen-specific antibody titers and cleared viable LASV from the tissues. These data support further development of ChAdOx1-Lassa-GPC and testing in non-human primate models of infection.Robert J. FischerJyothi N. PurushothamNeeltje van DoremalenSarah SebastianKimberly Meade-WhiteKathleen CordovaMichael LetkoM. Jeremiah MatsonFriederike FeldmannElaine HaddockRachel LaCasseGreg SaturdayTeresa LambeSarah C. GilbertVincent J. MunsterNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-11 (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 Robert J. Fischer Jyothi N. Purushotham Neeltje van Doremalen Sarah Sebastian Kimberly Meade-White Kathleen Cordova Michael Letko M. Jeremiah Matson Friederike Feldmann Elaine Haddock Rachel LaCasse Greg Saturday Teresa Lambe Sarah C. Gilbert Vincent J. Munster ChAdOx1-vectored Lassa fever vaccine elicits a robust cellular and humoral immune response and protects guinea pigs against lethal Lassa virus challenge
description	Abstract Lassa virus (LASV) infects hundreds of thousands of individuals each year, highlighting the need for the accelerated development of preventive, diagnostic, and therapeutic interventions. To date, no vaccine has been licensed for LASV. ChAdOx1-Lassa-GPC is a chimpanzee adenovirus-vectored vaccine encoding the Josiah strain LASV glycoprotein precursor (GPC) gene. In the following study, we show that ChAdOx1-Lassa-GPC is immunogenic, inducing robust T-cell and antibody responses in mice. Furthermore, a single dose of ChAdOx1-Lassa-GPC fully protects Hartley guinea pigs against morbidity and mortality following lethal challenge with a guinea pig-adapted LASV (strain Josiah). By contrast, control vaccinated animals reached euthanasia criteria 10–12 days after infection. Limited amounts of LASV RNA were detected in the tissues of vaccinated animals. Viable LASV was detected in only one animal receiving a single dose of the vaccine. A prime-boost regimen of ChAdOx1-Lassa-GPC in guinea pigs significantly increased antigen-specific antibody titers and cleared viable LASV from the tissues. These data support further development of ChAdOx1-Lassa-GPC and testing in non-human primate models of infection.
format	article
author	Robert J. Fischer Jyothi N. Purushotham Neeltje van Doremalen Sarah Sebastian Kimberly Meade-White Kathleen Cordova Michael Letko M. Jeremiah Matson Friederike Feldmann Elaine Haddock Rachel LaCasse Greg Saturday Teresa Lambe Sarah C. Gilbert Vincent J. Munster
author_facet	Robert J. Fischer Jyothi N. Purushotham Neeltje van Doremalen Sarah Sebastian Kimberly Meade-White Kathleen Cordova Michael Letko M. Jeremiah Matson Friederike Feldmann Elaine Haddock Rachel LaCasse Greg Saturday Teresa Lambe Sarah C. Gilbert Vincent J. Munster
author_sort	Robert J. Fischer
title	ChAdOx1-vectored Lassa fever vaccine elicits a robust cellular and humoral immune response and protects guinea pigs against lethal Lassa virus challenge
title_short	ChAdOx1-vectored Lassa fever vaccine elicits a robust cellular and humoral immune response and protects guinea pigs against lethal Lassa virus challenge
title_full	ChAdOx1-vectored Lassa fever vaccine elicits a robust cellular and humoral immune response and protects guinea pigs against lethal Lassa virus challenge
title_fullStr	ChAdOx1-vectored Lassa fever vaccine elicits a robust cellular and humoral immune response and protects guinea pigs against lethal Lassa virus challenge
title_full_unstemmed	ChAdOx1-vectored Lassa fever vaccine elicits a robust cellular and humoral immune response and protects guinea pigs against lethal Lassa virus challenge
title_sort	chadox1-vectored lassa fever vaccine elicits a robust cellular and humoral immune response and protects guinea pigs against lethal lassa virus challenge
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4667aaafa6c240a492ef4c7b8f637c7b
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ChAdOx1-vectored Lassa fever vaccine elicits a robust cellular and humoral immune response and protects guinea pigs against lethal Lassa virus challenge

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