title: Antigenicity and immunogenicity of a novel Plasmodium vivax circumsporozoite derived synthetic vaccine construct.
abstract: BACKGROUND
  The circumsporozoite (CS) protein is a major malaria sporozoite surface antigen currently being considered as vaccine candidate. Plasmodium vivax CS (PvCS) protein comprises a dimorphic central repeat fragment flanked by conserved regions that contain functional domains involved in parasite invasion of host cells. The protein amino (N-terminal) flank has a cleavage region (region I), essential for proteolytic processing prior to parasite invasion of liver cells.
  
  
  METHODS
  We have developed a 131-mer long synthetic polypeptide (LSP) named PvNR1R2 that includes the N-terminal flank and the two natural repeat variant regions known as VK210 and VK247. We studied the natural immune response to this region in human sera from different malaria-endemic areas and its immunogenicity in mice.
  
  
  RESULTS
  PvNR1R2 was more frequently recognized by sera from Papua New Guinea (PNG) (83%) than by samples from Colombia (24%) when tested by ELISA. The polypeptide formulated in Montanide ISA51 adjuvant elicited strong antibody responses in both C3H and CB6F1 mice strains. Antibodies from immunized mice as well as affinity-purified human IgG reacted with native protein by IFA test. Moreover, mouse immune sera induced strong (90%) in vitro inhibition of sporozoite invasion (ISI) of hepatoma cell lines.
  
  
  CONCLUSIONS
  These results encourage further studies in non-human primates to confirm the elicitation of sporozoite invasion blocking antibodies, to assess cell mediated immune responses and the protective efficacy of this polypeptide.
authors.affiliation: Malaria Vaccine and Drug Development Center (MVDC), Carrera 37 2Bis No. 5E-08, A.A. 25574, Cali, Colombia; Faculty of Health, University of Valle, Calle 4B # 36-00, Cali, Colombia.
authors.forename: Nora
authors.initials: N
authors.lastname: Céspedes
authors.affiliation: Malaria Vaccine and Drug Development Center (MVDC), Carrera 37 2Bis No. 5E-08, A.A. 25574, Cali, Colombia.
authors.forename: Eliécer
authors.initials: E
authors.lastname: Jiménez
authors.affiliation: Malaria Vaccine and Drug Development Center (MVDC), Carrera 37 2Bis No. 5E-08, A.A. 25574, Cali, Colombia; Caucaseco Scientific Research Centre, A.A. 760042, Cali, Colombia.
authors.forename: Mary
authors.initials: M
authors.lastname: Lopez-Perez
authors.affiliation: Malaria Vaccine and Drug Development Center (MVDC), Carrera 37 2Bis No. 5E-08, A.A. 25574, Cali, Colombia; Fundación Centro de Primates, AA 26020 Cali, Colombia.
authors.forename: Kelly
authors.initials: K
authors.lastname: Rubiano
authors.affiliation: Swiss Tropical and Public Health Institute, Socinstrasse 57, Basel, Switzerland.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Felger
authors.affiliation: Barcelona Centre for International Health Research (CRESIB, Hospital Clínic-Universitat de Barcelona), Barcelona, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Alonso
authors.affiliation: Malaria Vaccine and Drug Development Center (MVDC), Carrera 37 2Bis No. 5E-08, A.A. 25574, Cali, Colombia; Faculty of Health, University of Valle, Calle 4B # 36-00, Cali, Colombia.
authors.forename: Myriam
authors.initials: M
authors.lastname: Arévalo-Herrera
authors.affiliation: Biochemistry Department, University of Lausanne, 155 Ch. des Boveresses, 1066 Epalinges, Lausanne, Switzerland.
authors.forename: Giampietro
authors.initials: G
authors.lastname: Corradin
authors.affiliation: Malaria Vaccine and Drug Development Center (MVDC), Carrera 37 2Bis No. 5E-08, A.A. 25574, Cali, Colombia; Faculty of Health, University of Valle, Calle 4B # 36-00, Cali, Colombia. Electronic address: sherrera@inmuno.org.
authors.forename: Sócrates
authors.initials: S
authors.lastname: Herrera
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology; D045744:Cell Line, Tumor; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D056724:Immunity, Humoral; D017780:Malaria Vaccines / Q000276:immunology*; D016780:Malaria, Vivax / Q000517:prevention & control*; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D010966:Plasmodium vivax; D015800:Protozoan Proteins / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007106:Immune Sera; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan
keywords: CS protein; Long synthetic peptide; Malaria; Mice; Plasmodium vivax; Vaccine