title: Development of a chimeric Plasmodium berghei strain expressing the repeat region of the P. vivax circumsporozoite protein for in vivo evaluation of vaccine efficacy.
abstract: The 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 vitro culture systems and availability of animal models. Chimeric rodent Plasmodium parasites are safe and useful tools for the preclinical evaluation of new vaccine formulations. We report the successful development and characterization of chimeric Plasmodium berghei parasites bearing the type I repeat region of P. vivax circumsporozoite protein (CSP). The P. berghei-P. vivax chimeric 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. vivax CSP 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. vivax vaccines based on CSP.
authors.affiliation: Johns Hopkins Malaria Research Institute and Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Espinosa
authors.forename: Anjali
authors.initials: A
authors.lastname: Yadava
authors.forename: Evelina
authors.initials: E
authors.lastname: Angov
authors.forename: Paul L
authors.initials: PL
authors.lastname: Maurizio
authors.forename: Christian F
authors.initials: CF
authors.lastname: Ockenhouse
authors.forename: Fidel
authors.initials: F
authors.lastname: Zavala
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology; D002678:Chimera / Q000235:genetics* / Q000276:immunology; D019084:Fluorescent Antibody Technique, Indirect; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D010962:Plasmodium berghei / Q000235:genetics* / Q000276:immunology; D010966:Plasmodium vivax / Q000235:genetics* / Q000276:immunology; D015800:Protozoan Proteins / Q000235:genetics* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan