title: The N-terminal domain of Plasmodium falciparum circumsporozoite protein represents a target of protective immunity.
abstract: The N-terminal domain of the circumsporozoite protein (CSP) has been largely neglected in the search for a malaria vaccine in spite of being a target of inhibitory antibodies and protective T cell responses in mice. Thus, in order to develop this region as a vaccine candidate to be eventually associated with other candidates and, in particular, with the very advanced C-terminal counterpart, synthetic constructs representing N- and C-terminal regions of Plasmodium falciparum and Plasmodium berghei CSP were administered as single or combined formulations in mice. We show that the antisera generated against the combinations inhibit sporozoite invasion of hepatocytes in vitro better than antisera against single peptides. Furthermore, two different P. falciparum CSP N-terminal constructs (PfCS22-110 and PfCS65-110) were recognized by serum samples from people living in malaria-endemic regions. Importantly, recognition of the short N-terminal peptide (PfCS65-110) by sera from children living in a malaria-endemic region was associated with protection from disease. Taken together, these results underline the potential of using such fragments as malaria vaccine candidates.
authors.affiliation: Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.
authors.forename: Silayuv E
authors.initials: SE
authors.lastname: Bongfen
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Ntsama
authors.forename: Sandra
authors.initials: S
authors.lastname: Offner
authors.forename: Thomas
authors.initials: T
authors.lastname: Smith
authors.forename: Ingrid
authors.initials: I
authors.lastname: Felger
authors.forename: Marcel
authors.initials: M
authors.lastname: Tanner
authors.forename: Pedro
authors.initials: P
authors.lastname: Alonso
authors.forename: Issa
authors.initials: I
authors.lastname: Nebie
authors.forename: Jackeline F
authors.initials: JF
authors.lastname: Romero
authors.forename: Olivier
authors.initials: O
authors.lastname: Silvie
authors.forename: Ralph
authors.initials: R
authors.lastname: Torgler
authors.forename: Giampietro
authors.initials: G
authors.lastname: Corradin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D002675:Child, Preschool; D005260:Female; D022781:Hepatocytes / Q000469:parasitology; D006801:Humans; D008288:Malaria / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control; D017780:Malaria Vaccines; D016778:Malaria, Falciparum / Q000175:diagnosis / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D010962:Plasmodium berghei / Q000276:immunology; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D010446:Peptide Fragments; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan