Clinical Assessment of a Recombinant Simian Adenovirus ChAd63: a potent new vaccine vector

O'Hara, Geraldine, Duncan, Christopher, Ewer, Katie, Collins, Katharine, Elias, Sean, Halstead, Fenella, Goodman, Anna, Edwards, Nick, Reyes-Sandoval, Arturo, Bird, Prudence, Rowland, Rosalind, Sheehy, Susanne, Poulton, Ian, Hutchings, Claire, Todryk, Stephen, Andrews, Laura, Folgori, Antonella, Berrie, Eleanor, Moyle, Sarah, Nicosia, Alfredo, Colloca, Stefano, Cortese, Riccardo, Siani, Loredana, Lawrie, Alison, Gilbert, Sarah and Hill, Adrian (2012) Clinical Assessment of a Recombinant Simian Adenovirus ChAd63: a potent new vaccine vector. The Journal of Infectious Diseases, 205 (5). pp. 772-81. ISSN 0022-1899

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Official URL: http://dx.doi.org/10.1093/infdis/jir850

Abstract

Background
Vaccine development in human Plasmodium falciparum malaria has been hampered by the exceptionally high levels of CD8(+) T cells required for efficacy. Use of potently immunogenic human adenoviruses as vaccine vectors could overcome this problem, but these are limited by preexisting immunity to human adenoviruses.

Methods
From 2007 to 2010, we undertook a phase I dose and route
finding study of a new malaria vaccine, a replication-incompetent chimpanzee adenovirus 63 (ChAd63) encoding the preerythrocytic insert multiple epitope thrombospondin-related adhesion protein (ME-TRAP; n = 54 vaccinees) administered alone (n = 28) or with a modified vaccinia virus Ankara (MVA) ME-TRAP booster immunization 8 weeks later (n = 26). We observed an excellent safety profile. High levels of TRAP antigen-specific CD8(+) and CD4(+) T cells, as detected by interferon γ enzyme-linked immunospot assay and flow cytometry, were induced by intramuscular ChAd63 ME-TRAP immunization at doses of 5 × 10(10) viral particles and above. Subsequent administration of MVA ME-TRAP boosted responses to exceptionally high levels, and responses were maintained for up to 30 months postvaccination.

Conclusions
The ChAd63 chimpanzee adenovirus vector appears safe and highly immunogenic, providing a viable alternative to human adenoviruses as vaccine vectors for human use. Clinical Trials Registration. NCT00890019.

Item Type: Article
Uncontrolled Keywords: vaccine, malaria, T cells, trial
Subjects: B900 Others in Subjects allied to Medicine
C900 Others in Biological Sciences
Department: Faculties > Health and Life Sciences > School of Life Sciences > Applied Sciences
Depositing User: Ay Okpokam
Date Deposited: 28 Feb 2012 15:26
Last Modified: 10 Aug 2015 11:37
URI: http://nrl.northumbria.ac.uk/id/eprint/5536

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