Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge

Daphne A. Stanley; Anna N. Honko; Clement Asiedu; John C. Trefry; Annie W. Lau-Kilby; Joshua C. Johnson; Lisa Hensley; Virginia Ammendola; Adele Abbate; Fabiana Grazioli; Kathryn E. Foulds; Cheng Cheng; Lingshu Wang; Mitzi M. Donaldson; Stefano Colloca; Antonella Folgori; Mario Roederer; Gary J. Nabel; John Mascola; Alfredo Nicosia; Riccardo Cortese; Richard A. Koup; Nancy J. Sullivan

doi:10.1038/nm.3702

Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge

Daphne A. Stanley, Anna N. Honko, Clement Asiedu, John C. Trefry, Annie W. Lau-Kilby, Joshua C. Johnson, Lisa Hensley, Virginia Ammendola, Adele Abbate, Fabiana Grazioli, Kathryn E. Foulds, Cheng Cheng, Lingshu Wang, Mitzi M. Donaldson, Stefano Colloca, Antonella Folgori, Mario Roederer, Gary J. Nabel, John Mascola, Alfredo NicosiaRiccardo Cortese, Richard A. Koup, Nancy J. Sullivan

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243 Scopus citations

Abstract

Ebolavirus disease causes high mortality, and the current outbreak has spread unabated through West Africa. Human adenovirus type 5 vectors (rAd5) encoding ebolavirus glycoprotein (GP) generate protective immunity against acute lethal Zaire ebolavirus (EBOV) challenge in macaques, but fail to protect animals immune to Ad5, suggesting natural Ad5 exposure may limit vaccine efficacy in humans. Here we show that a chimpanzee-derived replication-defective adenovirus (ChAd) vaccine also rapidly induced uniform protection against acute lethal EBOV challenge in macaques. Because protection waned over several months, we boosted ChAd3 with modified vaccinia Ankara (MVA) and generated, for the first time, durable protection against lethal EBOV challenge.

Original language	English (US)
Pages (from-to)	1126-1129
Number of pages	4
Journal	Nature Medicine
Volume	20
Issue number	10
DOIs	https://doi.org/10.1038/nm.3702
State	Published - Oct 1 2014
Externally published	Yes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Medicine(all)

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Stanley, D. A., Honko, A. N., Asiedu, C., Trefry, J. C., Lau-Kilby, A. W., Johnson, J. C., Hensley, L., Ammendola, V., Abbate, A., Grazioli, F., Foulds, K. E., Cheng, C., Wang, L., Donaldson, M. M., Colloca, S., Folgori, A., Roederer, M., Nabel, G. J., Mascola, J., ... Sullivan, N. J. (2014). Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge. Nature Medicine, 20(10), 1126-1129. https://doi.org/10.1038/nm.3702

Stanley, DA, Honko, AN, Asiedu, C, Trefry, JC, Lau-Kilby, AW, Johnson, JC, Hensley, L, Ammendola, V, Abbate, A, Grazioli, F, Foulds, KE, Cheng, C, Wang, L, Donaldson, MM, Colloca, S, Folgori, A, Roederer, M, Nabel, GJ, Mascola, J, Nicosia, A, Cortese, R, Koup, RA & Sullivan, NJ 2014, 'Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge', Nature Medicine, vol. 20, no. 10, pp. 1126-1129. https://doi.org/10.1038/nm.3702

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abstract = "Ebolavirus disease causes high mortality, and the current outbreak has spread unabated through West Africa. Human adenovirus type 5 vectors (rAd5) encoding ebolavirus glycoprotein (GP) generate protective immunity against acute lethal Zaire ebolavirus (EBOV) challenge in macaques, but fail to protect animals immune to Ad5, suggesting natural Ad5 exposure may limit vaccine efficacy in humans. Here we show that a chimpanzee-derived replication-defective adenovirus (ChAd) vaccine also rapidly induced uniform protection against acute lethal EBOV challenge in macaques. Because protection waned over several months, we boosted ChAd3 with modified vaccinia Ankara (MVA) and generated, for the first time, durable protection against lethal EBOV challenge.",

author = "Stanley, {Daphne A.} and Honko, {Anna N.} and Clement Asiedu and Trefry, {John C.} and Lau-Kilby, {Annie W.} and Johnson, {Joshua C.} and Lisa Hensley and Virginia Ammendola and Adele Abbate and Fabiana Grazioli and Foulds, {Kathryn E.} and Cheng Cheng and Lingshu Wang and Donaldson, {Mitzi M.} and Stefano Colloca and Antonella Folgori and Mario Roederer and Nabel, {Gary J.} and John Mascola and Alfredo Nicosia and Riccardo Cortese and Koup, {Richard A.} and Sullivan, {Nancy J.}",

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AU - Stanley, Daphne A.

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AU - Asiedu, Clement

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AU - Lau-Kilby, Annie W.

AU - Johnson, Joshua C.

AU - Hensley, Lisa

AU - Ammendola, Virginia

AU - Abbate, Adele

AU - Grazioli, Fabiana

AU - Foulds, Kathryn E.

AU - Cheng, Cheng

AU - Wang, Lingshu

AU - Donaldson, Mitzi M.

AU - Colloca, Stefano

AU - Folgori, Antonella

AU - Roederer, Mario

AU - Nabel, Gary J.

AU - Mascola, John

AU - Nicosia, Alfredo

AU - Cortese, Riccardo

AU - Koup, Richard A.

AU - Sullivan, Nancy J.

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Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge

Abstract

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