Malaria is caused by complex protozoan Plasmodium parasites that have foiled efforts to develop a protective vaccine. Despite this, it has been known for more than 40 years that immunization with radiation-attenuated, whole Plasmodium sporozoites confers complete protection against malaria challenge. This model gave the rationale for development of recombinant and vectored subunit vaccination strategies that have, however, not yet matched whole sporozoite protective efficacy. Novel attenuation and immunization approaches for whole sporozoite vaccination and a deeper understanding of cellular and humoral protective immune responses that eliminate pre-erythrocytic stages are paving the way for the development of next-generation vaccination strategies that completely prevent malaria.
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