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

Abstract

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 preimmunization with Δhmgb2PbNK65 parasitized red blood cells that confer long-lasting protection in a murine experimental cerebral malaria model against two highly pathogenic homologous and heterologous parasites.

Live attenuated vaccines, a favorable strategy to provide long-term immunity against protozoan diseases

“…These and other blood-stage candidates (reviewed in [36]) have been shown to be highly immunogenic and protective against both homologous and heterologous challenge with different parasite strains (Table 1), although the persistence of high levels of parasitemia after immunization raises some concerns about their biosafety. Further GAP strategies and recent vaccine candidates intend to improve the attenuated phenotype of whole blood-stage parasites, boost T and B cell responses, and induce cross-stage, cross-species and long-lasting immunity [56,57].…”