Agnes Mwakingwe-Omari and colleagues used an established experimental approach to induce protection against the pre-erythrocytic stage of Plasmodium falciparum. Aseptic, purified and cryopreserved P. falciparum sporozoites were used to immunize naive volunteers who received chloroquine or pyrimethamine prophylaxis. The study demonstrates that immunization with sporozoites that infect the liver and at least partially replicate confers durable protection against infection and this protection is superior to the protection achieved with irradiated sporozoites that do not replicate. A substantial increase in protection can be achieved by varying the time and dose of the injected parasites, and sterilizing immunity against a heterologous strain was maintained for at least 3 months after vaccination. This is important as the vaccine must protect against a diversity of naturally circulating P. falciparum strains. The findings suggest that the vaccine may be suitable to confer broadly protective sterilizing immunity in the real-world settings.
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