Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation

Katie J. Ewer (), Geraldine A. O’Hara, Christopher J. A. Duncan, Katharine A. Collins, Susanne H. Sheehy, Arturo Reyes-Sandoval, Anna L. Goodman, Nick J. Edwards, Sean C. Elias, Fenella D. Halstead, Rhea J. Longley, Rosalind Rowland, Ian D. Poulton, Simon J. Draper, Andrew M. Blagborough, Eleanor Berrie, Sarah Moyle, Nicola Williams, Loredana Siani, Antonella Folgori, Stefano Colloca, Robert E. Sinden, Alison M. Lawrie, Riccardo Cortese, Sarah C. Gilbert, Alfredo Nicosia and Adrian V. S. Hill
Additional contact information
Katie J. Ewer: The Jenner Institute Laboratories, University of Oxford
Geraldine A. O’Hara: Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital
Christopher J. A. Duncan: Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital
Katharine A. Collins: The Jenner Institute Laboratories, University of Oxford
Susanne H. Sheehy: Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital
Arturo Reyes-Sandoval: The Jenner Institute Laboratories, University of Oxford
Anna L. Goodman: The Jenner Institute Laboratories, University of Oxford
Nick J. Edwards: The Jenner Institute Laboratories, University of Oxford
Sean C. Elias: The Jenner Institute Laboratories, University of Oxford
Fenella D. Halstead: The Jenner Institute Laboratories, University of Oxford
Rhea J. Longley: The Jenner Institute Laboratories, University of Oxford
Rosalind Rowland: Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital
Ian D. Poulton: Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital
Simon J. Draper: The Jenner Institute Laboratories, University of Oxford
Andrew M. Blagborough: Imperial College London
Eleanor Berrie: Clinical Biomanufacturing Facility, University of Oxford, Churchill Hospital
Sarah Moyle: Clinical Biomanufacturing Facility, University of Oxford, Churchill Hospital
Nicola Williams: Centre for Statistics in Medicine
Loredana Siani: Okairos
Antonella Folgori: Okairos
Stefano Colloca: Okairos
Robert E. Sinden: The Jenner Institute Laboratories, University of Oxford
Alison M. Lawrie: Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital
Riccardo Cortese: Okairos
Sarah C. Gilbert: The Jenner Institute Laboratories, University of Oxford
Alfredo Nicosia: Okairos
Adrian V. S. Hill: The Jenner Institute Laboratories, University of Oxford

Nature Communications, 2013, vol. 4, issue 1, 1-10

Abstract: Abstract Induction of antigen-specific CD8+ T cells offers the prospect of immunization against many infectious diseases, but no subunit vaccine has induced CD8+ T cells that correlate with efficacy in humans. Here we demonstrate that a replication-deficient chimpanzee adenovirus vector followed by a modified vaccinia virus Ankara booster induces exceptionally high frequency T-cell responses (median >2400 SFC/106 peripheral blood mononuclear cells) to the liver-stage Plasmodium falciparum malaria antigen ME-TRAP. It induces sterile protective efficacy against heterologous strain sporozoites in three vaccinees (3/14, 21%), and delays time to patency through substantial reduction of liver-stage parasite burden in five more (5/14, 36%), P=0.008 compared with controls. The frequency of monofunctional interferon-γ-producing CD8+ T cells, but not antibodies, correlates with sterile protection and delay in time to patency (Pcorrected=0.005). Vaccine-induced CD8+ T cells provide protection against human malaria, suggesting that a major limitation of previous vaccination approaches has been the insufficient magnitude of induced T cells.

Date: 2013
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DOI: 10.1038/ncomms3836

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