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Heterologous prime-boost vaccination has been shown to be an efficient way of inducing T cell responses in animals and in humans. We have used three vaccine vectors, naked DNA, modified vaccinia virus Ankara (MVA), and attenuated fowlpox strain, FP9, for prime-boost vaccination approaches against Plasmodium falciparum malaria in humans. In this study, we characterize, using two types of ELISPOT assays and FACS analysis, cell-mediated immune responses induced by different prime-boost combinations where all vectors encode a multiepitope string fused to the pre-erythrocytic Ag thrombospondin-related adhesion protein. We show that these different vectors need to be used in a specific order for an optimal ex vivo IFN-gamma response. From the different combinations, DNA priming followed by MVA boosting and FP9 priming followed by MVA boosting were most immunogenic and in both cases the IFN-gamma response was of broad specificity and cross-reactive against two P. falciparum strains (3D7 and T9/96). Immunization with all three vectors showed no improvement over optimal two vector regimes. Strong ex vivo IFN-gamma responses peaked 1 wk after the booster dose, but cultured ELISPOT assays revealed longer-lasting T cell memory responses for at least 6 mo. In the DNA-primed vaccinees the IFN-gamma response was mainly due to CD4(+) T cells, whereas in the FP9-primed vaccinees it was mainly due to CD4-dependent CD8(+) T cells. This difference may be of importance for the protective efficacy of these vaccination approaches against various diseases.

Original publication

DOI

10.4049/jimmunol.174.1.449

Type

Journal article

Journal

J Immunol

Publication Date

01/01/2005

Volume

174

Pages

449 - 455

Keywords

Animals, Epitopes, B-Lymphocyte, Epitopes, T-Lymphocyte, Flow Cytometry, Fowlpox virus, Genetic Vectors, Humans, Interferon-gamma, Lymphocyte Subsets, Malaria, Falciparum, Plasmodium falciparum, Protozoan Proteins, T-Lymphocytes, Vaccines, Attenuated, Vaccines, DNA, Vaccinia virus, Viral Vaccines