Following on from the recent post about the promise and potential pitfalls of adenovirus-based vaccine vectors, an open access paper published on Tuesday in the Journal of Infectious Diseases reports data that appear to fall firmly on the promise side of the balance sheet. Researchers from the laboratory of Adrian Hill at the University of Oxford describe results of a phase I trial of a chimpanzee adenovirus type 63 (ChAd63) vector encoding malaria antigens, showing that the vaccine induced CD8 and CD4 T cell responses in all recipients. The magnitude of the responses (as measured by ELISPOT assays) was also impressive; the researchers note they were superior to those observed with Merck’s Ad5-based HIV vaccine candidate. Safety compared favorably to other adenovirus vectors.
Unlike the phase I trial of chimpanzee Ad3 as a hepatitis C vaccine covered in the prior post, which excluded anyone with antibody titers against the vector of >1:200, the malaria study enrolled a cohort of ten individuals with no restrictions on baseline titers of antibodies to the ChAd63 vector. The researchers analyzed this cohort and found no correlation between the presence of anti-vector antibodies at baseline and reduced vaccine immunogenicity. These results, while requiring confirmation in larger numbers of participants, suggest that pre-existing immunity to the ChAd63 vector may not be a problem.
J Infect Dis. (2012) doi: 10.1093/infdis/jir850
First published online: January 24, 2012
Geraldine A. O'Hara1,a, Christopher J. A. Duncan1,a, Katie J. Ewer1,a, Katharine A. Collins1, Sean C. Elias1, Fenella D. Halstead1, Anna L. Goodman1, Nick J. Edwards1, Arturo Reyes-Sandoval1, Prudence Bird2, Rosalind Rowland1, Susanne H. Sheehy1, Ian D. Poulton1, Claire Hutchings1, Stephen Todryk1, Laura Andrews1, Antonella Folgori1, Eleanor Berrie2, Sarah Moyle2, Alfredo Nicosia3,4, Stefano Colloca3, Riccardo Cortese3,4, Loredana Siani3, Alison M. Lawrie1, Sarah C. Gilbert1 and Adrian V. S. Hill1
1Centre for Clinical Vaccinology and Tropical Medicine and the Jenner Institute Laboratories, University of Oxford
2Clinical BioManufacturing Facility, Nuffield Department of Clinical Medicine, Churchill Hospital, University of Oxford, Headington, United Kingdom
3Okairos AG, Rome
4CEINGE, Naples, Italy
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 × 1010 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.