Progress in DNA-based heterologous prime-boost immunization strategies for malaria.

Journal article

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: Moore, A; Hill, A

• Publication status: Published
• Journal: Immunological reviews
• Volume: 199
• Issue: 1
• Pages: 126-143
• Publication date: 2004-06-01
• DOI: 10.1111/j.0105-2896.2004.00138.x
• EISSN: 1600-065X
• ISSN: 0105-2896
• Language: English
• Keywords: Immunization, Secondary; Genetic Vectors; Malaria; Vaccines, DNA; Epitopes, B-Lymphocyte; Humans; Vaccinia virus; Plasmodium; Epitopes, T-Lymphocyte; Malaria Vaccines; Peptides; Plasmids; CD8-Positive T-Lymphocytes; Animals