title: Expression and immunogenicity of the Plasmodium falciparum circumsporozoite protein: the role of GPI signal sequence.
abstract: Previous studies have shown that the immunogenicity of rodent malaria parasite-derived circumsporozoite protein (CS) can be improved by deleting the glycosyl-phosphatidyl-inositol (GPI) signal sequence. To study whether GPI signal sequence deletion would also improve immunogenicity of CS derived from the major plasmodium species causing mortality in humans (P. falciparum), we tested different variants of the P. falciparum CS protein in the context of a live vector-based vaccine carrier (rAd35). We demonstrate that deletion of the GPI signal sequence from CS did not result in altered expression or secretion. In contrast, cellular localization was clearly altered, which perhaps helps to explain the significant improvement of anti-CS antibody and T-cell responses observed in mice using deletion variants in the context of the rAd35 carrier. Our results show that rational design of antigens is warranted for further development of malaria vaccines.
authors.affiliation: Crucell Holland BV, P.O. Box 2048, Leiden 2301 CA, The Netherlands.
authors.forename: Olga J A E
authors.initials: OJ
authors.lastname: Ophorst
authors.forename: Katarina
authors.initials: K
authors.lastname: Radosević
authors.forename: Krista
authors.initials: K
authors.lastname: Ouwehand
authors.forename: Wouter
authors.initials: W
authors.lastname: van Beem
authors.forename: Ratna
authors.initials: R
authors.lastname: Mintardjo
authors.forename: Jeroen
authors.initials: J
authors.lastname: Sijtsma
authors.forename: Jorn
authors.initials: J
authors.lastname: Kaspers
authors.forename: Arjen
authors.initials: A
authors.lastname: Companjen
authors.forename: Lennart
authors.initials: L
authors.lastname: Holterman
authors.forename: Jaap
authors.initials: J
authors.lastname: Goudsmit
authors.forename: Menzo J E
authors.initials: MJ
authors.lastname: Havenga
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D005260:Female; D017353:Gene Deletion; D017261:Glycosylphosphatidylinositols / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D021382:Protein Sorting Signals / Q000235:genetics / Q000502:physiology*; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D017261:Glycosylphosphatidylinositols; D017780:Malaria Vaccines; D021382:Protein Sorting Signals; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan