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

Geraldine O'Hara, Christopher Duncan, Katie Ewer, Katharine Collins, Sean Elias, Fenella Halstead, Anna Goodman, Nick Edwards, Arturo Reyes-Sandoval, Prudence Bird, Rosalind Rowland, Susanne Sheehy, Ian Poulton, Claire Hutchings, Stephen Todryk, Laura Andrews, Antonella Folgori, Eleanor Berrie, Sarah Moyle, Alfredo NicosiaStefano Colloca, Riccardo Cortese, Loredana Siani, Alison Lawrie, Sarah Gilbert, Adrian Hill

Research output: Contribution to journalArticlepeer-review

164 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)772-81
JournalThe Journal of Infectious Diseases
Volume205
Issue number5
DOIs
Publication statusPublished - 2012

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