title: Progress in DNA-based heterologous prime-boost immunization strategies for malaria.
abstract: An effective vaccine against malaria is urgently required to relieve the immense human suffering and mortality caused by this parasite. A successful subunit vaccine against the liver stage of malaria will require the induction of high levels of protective T cells. Despite success in small animal models, DNA vaccines fail to induce strong cellular immune responses in humans. However, DNA vaccines can induce a T-cell response that can be strongly boosted by recombinant viral vectors. We have evaluated this heterologous prime-boost approach using the Plasmodium berghei mouse model for immunogenicity and protective efficacy against malaria challenge using combinations of plasmid DNA, recombinant modified vaccinia virus Ankara, fowlpox virus, and non-replicating adenovirus. We have proceeded to test immunogenicity and efficacy of successful heterologous prime-boost vaccines in phase I/IIa trials in malaria naïve subjects in the UK and in semi-immune individuals in The Gambia. In these clinical trials, remarkably high levels of effector T-cell responses have been induced and significant protection documented in a human sporozoite challenge model. We summarize the preclinical design and development of these heterologous prime-boost vaccines and discuss the encouraging results that have been observed in vaccinated humans.
authors.affiliation: Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK. anne.moore@ndm.ox.ac.uk
authors.forename: Anne C
authors.initials: AC
authors.lastname: Moore
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary; D008288:Malaria / Q000276:immunology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology; D010455:Peptides / Q000276:immunology; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D010961:Plasmodium / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology
chemical_list: D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D017780:Malaria Vaccines; D010455:Peptides; D019444:Vaccines, DNA