Expression and immunogenicity of the Plasmodium falciparum circumsporozoite protein: the role of GPI signal sequence.
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.
Ophorst
Olga J A E
OJ
Crucell Holland BV, P.O. Box 2048, Leiden 2301 CA, The Netherlands.
Radosević
Katarina
K
Ouwehand
Krista
K
van Beem
Wouter
W
Mintardjo
Ratna
R
Sijtsma
Jeroen
J
Kaspers
Jorn
J
Companjen
Arjen
A
Holterman
Lennart
L
Goudsmit
Jaap
J
Havenga
Menzo J E
MJ
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
D017261:Glycosylphosphatidylinositols; D017780:Malaria Vaccines; D021382:Protein Sorting Signals; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan