Development of a Chimeric Plasmodium bergheiStrain Expressing the Repeat Region of the P. vivaxCircumsporozoite Protein for In VivoEvaluation of Vaccine Efficacy

ABSTRACTThe development of vaccine candidates against Plasmodium vivax—the most geographically widespread human malaria species—is challenged by technical difficulties, such as the lack of in vitroculture systems and availability of animal models. Chimeric rodent Plasmodiumparasites are safe and useful tools for the preclinical evaluation of new vaccine formulations. We report the successful development and characterization of chimeric Plasmodium bergheiparasites bearing the type I repeat region of P. vivaxcircumsporozoite protein (CSP). The P. berghei-P. vivaxchimeric strain develops normally in mosquitoes and produces highly infectious sporozoites that produce patent infection in mice that are exposed to the bites of as few as 3 P. berghei-P. vivax-infected mosquitoes. Using this transgenic parasite, we demonstrate that monoclonal and polyclonal antibodies against P. vivaxCSP strongly inhibit parasite infection and thus support the notion that these antibodies play an important role in protective immunity. The chimeric parasites we developed represent a robust model for evaluating protective immune responses against P. vivaxvaccines based on CSP.