1. Protective CD8(+) T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation
- Author
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Adrian V. S. Hill, Sarah C. Gilbert, Loredana Siani, Rhea J. Longley, Alison M. Lawrie, Rosalind Rowland, Katharine A. Collins, Christopher J A Duncan, Riccardo Cortese, Sarah Moyle, Sean C. Elias, Alfredo Nicosia, Fenella D. Halstead, Ian D. Poulton, Eleanor Berrie, Nick J. Edwards, Geraldine O'Hara, Susanne H. Sheehy, Robert E. Sinden, Anna L. Goodman, Antonella Folgori, Arturo Reyes-Sandoval, Nicola Williams, Simon J. Draper, Andrew M. Blagborough, Stefano Colloca, Katie J. Ewer, 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, and Hill, Av
- Subjects
INFLUENZA-VIRUS ,Male ,Protozoan Proteins ,General Physics and Astronomy ,Antibodies, Protozoan ,CD8-Positive T-Lymphocytes ,chemistry.chemical_compound ,0302 clinical medicine ,DNA VACCINES ,Cytotoxic T cell ,030212 general & internal medicine ,Malaria, Falciparum ,0303 health sciences ,Immunity, Cellular ,Multidisciplinary ,biology ,NONHUMAN-PRIMATES ,Middle Aged ,3. Good health ,PHASE 2A TRIAL ,Science & Technology - Other Topics ,MEDIATED PROTECTION ,Female ,Antibody ,RHESUS-MONKEYS ,Adult ,Adolescent ,POLYMERASE-CHAIN-REACTION ,Genetic Vectors ,Plasmodium falciparum ,Immunization, Secondary ,Vaccinia virus ,VACCINIA VIRUS ANKARA ,Article ,General Biochemistry, Genetics and Molecular Biology ,DNA vaccination ,03 medical and health sciences ,Interferon-gamma ,Young Adult ,Immunity ,Malaria Vaccines ,MD Multidisciplinary ,Animals ,Humans ,030304 developmental biology ,NAIVE ADULTS ,Science & Technology ,MULTIDISCIPLINARY SCIENCES ,CD8 ,General Chemistry ,biology.organism_classification ,Virology ,Immunization ,chemistry ,PRIME-BOOST IMMUNIZATION ,Immunology ,biology.protein ,Leukocytes, Mononuclear ,Adenoviruses, Simian ,Vaccinia - 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., Induction of protective immunity mediated by CD8+ T cells has been a long sought goal in vaccinology. Here, Ewer et al. report induction of protective efficacy against Plasmodium falciparum malaria in a phase IIa prime-boost vaccine trial where efficacy correlates strongly with induced CD8 T-cell responses.
- Published
- 2013