Genetic vaccination approaches against malaria based on the circumsporozoite protein

Malaria is the world's major parasitic disease, for which effective control measures are urgently needed. Despite considerable efforts, no successful vaccine against malaria has been developed so far. The method of DNA-based immunization offers the possibility to induce both antibody- and cell-mediated immune responses to a variety of antigens. The flexibility of the DNA vaccine technology permits the combination of several antigens from different developmental stages of the parasite's complicated life cycle. This review covers the development of DNA-based immunization against malaria from initial experiments in small animals to recently conducted clinical studies. Focusing on one of the best characterized malaria vaccine candidate antigens, the circumsporozoite protein, an overview of strategies to enhance vaccine efficacy is provided. Advanced application methods such as the gene gun technology or the needle-less jet injection device are described. As DNA vaccination represents a relatively new methodology, safety concerns associated with planned clinical applications are discussed. In summary, this novel type of vaccine has to be considered as a promising tool for future malaria vaccination strategies.