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.
Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation / Ewer, Kj; O'Hara, Ga; Duncan, Cj; 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, Alfredo; Hill, Av. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 4:(2013), pp. 2836-2836. [10.1038/ncomms3836]
Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation.
NICOSIA, Alfredo;
2013
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/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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
