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J Infect Dis. 2012 Mar 1;205(5):772-81. doi: 10.1093/infdis/jir850. Epub 2012 Jan 24.

Clinical assessment of a recombinant simian adenovirus ChAd63: a potent new vaccine vector.

Author information

1
Centre for Clinical Vaccinology and Tropical Medicine and the Jenner Institute Laboratories, University of Oxford, UK. geraldine.ohara@ndm.ox.ac.uk

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.

PMID:
22275401
PMCID:
PMC3274376
DOI:
10.1093/infdis/jir850
[Indexed for MEDLINE]
Free PMC Article

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