C3d binding to the circumsporozoite protein carboxy-terminus deviates immunity against malaria
| Autor: | Josef Thalhamer, George C. Tsokos, Richard Weiss, David B. Winter, Evelina Angov, Elizabeth H. Duncan, Farhat Khan, Jeffrey A. Lyon, Jackie L. Williams, Wolfgang W. Leitner, Elke S. Bergmann-Leitner, Sandra Scheiblhofer, Defeng Chen |
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| Rok vydání: | 2005 |
| Předmět: |
Plasmodium berghei
Molecular Sequence Data Immunology Protozoan Proteins Antibodies Protozoan chemical and pharmacologic phenomena Biology Epitope DNA vaccination Mice Th2 Cells Immune system Immunity parasitic diseases Animals Immunology and Allergy Base Sequence Immunogenicity fungi General Medicine biology.organism_classification Virology Recombinant Proteins Malaria Circumsporozoite protein Complement C3d biology.protein Antibody Spleen |
| Zdroj: | International Immunology. 17:245-255 |
| ISSN: | 1460-2377 |
| DOI: | 10.1093/intimm/dxh205 |
| Popis: | The immunogenicity of recombinant protein or anti-viral DNA vaccines can be significantly improved by the addition of tandem copies of the complement fragment C3d. We sought to determine if the efficacy of a circumsporozoite protein (CSP)-based DNA vaccine delivered to mouse skin by gene gun was improved by using this strategy. Instead, we found that C3d suppressed the protective immunity against Plasmodium berghei malaria infection and deviated immunity, most notably by suppressing the induction of antibodies specific for the CSP C-terminal flanking sequence and by suppressing the induction of CSP-specific IL-4-producing spleen cells. We further showed that C3d bound to the C-terminal flanking sequence of the CSP, which may explain the immune deviation observed in CS/C3d chimeric antigen. We have thus identified C3d-mediated epitope masking and shifting of both the humoral and cellular immune responses as a potential novel escape mechanism, which plasmodia may use to divert the induction of protective immunity. |
| Databáze: | OpenAIRE |
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