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The Journal of Immunology, 2005, 174: 449-455.
Copyright © 2005 by The American Association of Immunologists

Differential Immunogenicity of Various Heterologous Prime-Boost Vaccine Regimens Using DNA and Viral Vectors in Healthy Volunteers1

Jenni M. Vuola2,*, Sheila Keating*, Daniel P. Webster*, Tamara Berthoud*, Susanna Dunachie*, Sarah C. Gilbert{dagger} and Adrian V. S. Hill3,*,{dagger}

* Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Medicine and {dagger} Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom

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.




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