title: Rapid identification of malaria vaccine candidates based on alpha-helical coiled coil protein motif.
abstract: To identify malaria antigens for vaccine development, we selected alpha-helical coiled coil domains of proteins predicted to be present in the parasite erythrocytic stage. The corresponding synthetic peptides are expected to mimic structurally "native" epitopes. Indeed the 95 chemically synthesized peptides were all specifically recognized by human immune sera, though at various prevalence. Peptide specific antibodies were obtained both by affinity-purification from malaria immune sera and by immunization of mice. These antibodies did not show significant cross reactions, i.e., they were specific for the original peptide, reacted with native parasite proteins in infected erythrocytes and several were active in inhibiting in vitro parasite growth. Circular dichroism studies indicated that the selected peptides assumed partial or high alpha-helical content. Thus, we demonstrate that the bioinformatics/chemical synthesis approach described here can lead to the rapid identification of molecules which target biologically active antibodies, thus identifying suitable vaccine candidates. This strategy can be, in principle, extended to vaccine discovery in a wide range of other pathogens.
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: Viviane
authors.initials: V
authors.lastname: Villard
authors.forename: George W
authors.initials: GW
authors.lastname: Agak
authors.forename: Géraldine
authors.initials: G
authors.lastname: Frank
authors.forename: Ali
authors.initials: A
authors.lastname: Jafarshad
authors.forename: Catherine
authors.initials: C
authors.lastname: Servis
authors.forename: Issa
authors.initials: I
authors.lastname: Nébié
authors.forename: Sodiomon B
authors.initials: SB
authors.lastname: Sirima
authors.forename: Ingrid
authors.initials: I
authors.lastname: Felger
authors.forename: Myriam
authors.initials: M
authors.lastname: Arevalo-Herrera
authors.forename: Socrates
authors.initials: S
authors.lastname: Herrera
authors.forename: Frederic
authors.initials: F
authors.lastname: Heitz
authors.forename: Volker
authors.initials: V
authors.lastname: Bäcker
authors.forename: Pierre
authors.initials: P
authors.lastname: Druilhe
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Kajava
authors.forename: Giampietro
authors.initials: G
authors.lastname: Corradin
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D002942:Circular Dichroism; D004797:Enzyme-Linked Immunosorbent Assay; D019084:Fluorescent Antibody Technique, Indirect / Q000379:methods; D016678:Genome; D006801:Humans; D017780:Malaria Vaccines / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D010961:Plasmodium / Q000235:genetics*; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D010446:Peptide Fragments; D010455:Peptides; D015800:Protozoan Proteins