Protective CD8 + T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation
Ewer KJ., O'Hara GA., Duncan CJA., Collins KA., Sheehy SH., Reyes-Sandoval A., Goodman AL., Edwards NJ., Elias SC., Halstead FD., Longley RJ., Rowland R., Poulton ID., Draper SJ., Blagborough AM., Berrie E., Moyle S., Williams N., Siani L., Folgori A., Colloca S., Sinden RE., Lawrie AM., Cortese R., Gilbert SC., Nicosia A., Hill AVS.
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/10 6 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 (P corrected =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. © 2013 Macmillan Publishers Limited. All rights reserved.