Protective immunity induced by daily bites from irradiated mosquitoes infected with Plasmodium yoelii

Individuals in malaria endemic regions do not develop fully protective immune responses against Plasmodium liver stage infections. In high transmission areas, individuals can be exposed to more than two infective mosquito bites daily. Their exposure to Plasmodium sporozoites, therefore, is in the form of small and frequent doses. This is very different from individuals studied in controlled immunization trials where the delivery of large numbers of radiation-attenuated sporozoites in a limited number of doses can induce sterile protective immunity. Using irradiated mosquitoes infected with Plasmodium yoelii 17XNL, we tested whether daily bites from a few mosquitoes can induce a protective immune response in mice. This immunization strategy successfully induced a protective response, preventing the development of liver stages when mice were challenged with nonirradiated sporozoites. These results provide further support for the development of liver stage vaccines. They are also a call for further study into why fully protective responses against the liver stage are not seen in individuals from endemic regions.