Progress in DNA‐based heterologous prime‐boost immunization strategies for malaria

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Abstract
Summary:  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.