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Due to the lack of efficiency to control malaria elicited by sub-unit vaccine preparations, vaccination with live-attenuated  Plasmodium  parasite as reported 70 years ago with irradiated sporozoites regained recently a significant interest. The complex life cycle of the parasite and the different stages of development between mammal host and anopheles do not help to propose an easy vaccine strategy. In order to achieve a complete long-lasting protection against  Plasmodium  infection and disease, we considered a genetically attenuated blood stage parasite in the  hmgb2 gene  coding for the high-mobility-group-box 2 (HMGB2). This  Plasmodium  protein belongs to the HMGB family and hold as the mammal proteins, a double life since it acts first as a nuclear factor involved in chromatin remodelling and transcription regulation and second, when secreted as an active pro-inflammatory alarmin protein. Even though the number of reports on whole living attenuated blood stage parasites is limited when compared to attenuated sporozoites, the results reported with  Plasmodium  KO parasites are very encouraging. In this report, we present a novel strategy based on pre-immunization with  Δhmgb2Pb NK65 parasitized red blood cells that confer long-lasting protection in a murine experimental cerebral malaria model against two highly pathogenic homologous and heterologous parasites.

A genetically hmgb2 attenuated blood stage P. berghei induces crossed-long live protection