title: A highly infectious Plasmodium yoelii parasite, bearing Plasmodium falciparum circumsporozoite protein.
abstract: BACKGROUND
  Plasmodium circumsporozoite protein (CSP) is a major surface antigen present in the sporozoite (Spz) stage of a malaria parasite. RTS, S vaccine, the most clinically advanced malaria vaccine, consists of a large portion of Plasmodium falciparum CSP (PfCSP). A highly infectious, recombinant rodent malaria, Plasmodium yoelii parasite bearing a full-length PfCSP, PfCSP/Py Spz, was needed as a tool to evaluate the role of PfCSP in mediating, protective, anti-malaria immunity in a mouse model.
  
  
  METHODS
  A transgenic parasite, PfCSP/Py Spz, was generated by inserting a construct expressing the PfCSP at the locus of the P. yoelii CSP gene by double cross-over homologous recombination. Then the biological and protective properties of PfCSP/Py Spz were determined.
  
  
  RESULTS
  This PfCSP/Py parasite produced up to 30,000 Spz in mosquito salivary glands, which is equal or even higher than the number of Spz produced by wild-type P. yoelii parasites. Five bites of PfCSP/Py-infected mosquitoes could induce blood infection in BALB/c mice.
  
  
  CONCLUSIONS
  The current study has demonstrated a successful establishment of a transgenic P. yoelii parasite clone that is able to express a full-length PfCSP, PfCSP/Py parasite. Importantly, this PfCSP/Py parasite can be as infectious as the wild-type P. yoelii parasite both in mosquito vector and in mouse, a mammalian host. A new transgenic parasite that expresses a full-length PfCSP may become a useful tool for researchers to investigate immunity against PfCSP in a mouse model.
authors.affiliation: HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY, USA.|Department of Pathology, New York University School of Medicine, New York, NY, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Medical Zoology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Kaneko
authors.affiliation: HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Tsao
authors.affiliation: Division of Parasitology, Department of Microbiology, New York University School of Medicine, New York, NY, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Mitchell
authors.affiliation: Division of Parasitology, Department of Microbiology, New York University School of Medicine, New York, NY, USA.
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Nardin
authors.affiliation: Department of Medical Zoology, Mie University Graduate School of Medicine, Tsu, Mie, Japan. iwanaga@doc.medic.mie-u.ac.jp.
authors.forename: Shiroh
authors.initials: S
authors.lastname: Iwanaga
authors.affiliation: Department of Medical Zoology, Mie University Graduate School of Medicine, Tsu, Mie, Japan. m-yuda@doc.medic.mie-u.ac.jp.
authors.forename: Masao
authors.initials: M
authors.lastname: Yuda
authors.affiliation: HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY, USA. mtsuji@adarc.org.
authors.forename: Moriya
authors.initials: M
authors.lastname: Tsuji
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D009033:Culicidae / Q000469:parasitology*; D004195:Disease Models, Animal; D005260:Female; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D030781:Organisms, Genetically Modified / Q000235:genetics / Q000276:immunology; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D010967:Plasmodium yoelii / Q000235:genetics* / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics* / Q000276:immunology*; D012469:Salivary Glands / Q000469:parasitology; D013601:T-Lymphocytes / Q000469:parasitology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan
keywords: Circumsporozoite protein; PfCSP/Py; Plasmodium falciparum; Plasmodium yoelii