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

Nat Med. 2014 Oct;20(10):1126-9. doi: 10.1038/nm.3702. Epub 2014 Sep 7.

Authors

Daphne A Stanley¹, Anna N Honko², Clement Asiedu³, John C Trefry⁴, Annie W Lau-Kilby¹, Joshua C Johnson², Lisa Hensley², Virginia Ammendola⁵, Adele Abbate⁵, Fabiana Grazioli⁵, Kathryn E Foulds¹, Cheng Cheng¹, Lingshu Wang¹, Mitzi M Donaldson¹, Stefano Colloca⁵, Antonella Folgori⁵, Mario Roederer¹, Gary J Nabel⁶, John Mascola¹, Alfredo Nicosia⁷, Riccardo Cortese⁸, Richard A Koup¹, Nancy J Sullivan¹

Affiliations

¹ Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
² 1] United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA. [2] Integrated Research Facility, NIAID, NIH, Fort Detrick, Maryland, USA (A.N.H., J.C.J. and L.H.), and Sanofi, Cambridge, Massachusetts, USA (G.J.N.).
³ 1] Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA. [2].
⁴ United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
⁵ Okairos, Rome, Italy.
⁶ 1] Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA. [2] Integrated Research Facility, NIAID, NIH, Fort Detrick, Maryland, USA (A.N.H., J.C.J. and L.H.), and Sanofi, Cambridge, Massachusetts, USA (G.J.N.).
⁷ 1] Okairos, Rome, Italy. [2] Centro Ingegneria Genetica (CEINGE), Naples, Italy. [3] Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
⁸ Keires AG, Basel, Switzerland.

PMID: 25194571
DOI: 10.1038/nm.3702

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.

Publication types

Research Support, N.I.H., Intramural

MeSH terms

Adenovirus Vaccines / administration & dosage
Adenovirus Vaccines / genetics
Adenovirus Vaccines / immunology
Adenoviruses, Human / genetics
Adenoviruses, Human / immunology
Adenoviruses, Simian / genetics
Adenoviruses, Simian / immunology
Animals
Defective Viruses / genetics
Defective Viruses / immunology
Ebola Vaccines / administration & dosage
Ebola Vaccines / genetics
Ebola Vaccines / immunology*
Ebolavirus / genetics
Ebolavirus / immunology*
Female
Genetic Vectors
Hemorrhagic Fever, Ebola / immunology*
Hemorrhagic Fever, Ebola / prevention & control*
Hemorrhagic Fever, Ebola / virology
Humans
Immunization, Secondary
Macaca fascicularis
Pan troglodytes
RNA, Viral / blood
RNA, Viral / genetics
Time Factors
Vaccinia virus / genetics
Vaccinia virus / immunology

Substances

Adenovirus Vaccines
Ebola Vaccines
RNA, Viral

Grants and funding

Intramural NIH HHS/United States