Expression and immunogenicity of the Plasmodium falciparum circumsporozoite protein: the role of GPI signal sequence
| Autor: | Jaap Goudsmit, Katarina Radosevic, Olga J.A.E Ophorst, Lennart Holterman, Ratna Mintardjo, Arjen Companjen, Krista Ouwehand, Menzo J. E. Havenga, Jorn Kaspers, Jeroen Sijtsma, Wouter van Beem |
|---|---|
| Přispěvatelé: | Amsterdam institute for Infection and Immunity, General Internal Medicine |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Signal peptide
Glycosylphosphatidylinositols T-Lymphocytes Molecular Sequence Data Plasmodium falciparum Protozoan Proteins Context (language use) Protein Sorting Signals Adenoviridae Mice Antigen Cell Line Tumor Malaria Vaccines parasitic diseases Animals Humans Amino Acid Sequence Cellular localization B-Lymphocytes General Veterinary General Immunology and Microbiology biology Immunogenicity Public Health Environmental and Occupational Health biology.organism_classification Virology Circumsporozoite protein Infectious Diseases biology.protein Mice Inbred CBA Molecular Medicine Female Antibody Gene Deletion |
| Zdroj: | Vaccine, 25(8), 1426-1436. Elsevier BV |
| ISSN: | 0264-410X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect