Antibodies to Escherichia coli-Expressed C-Terminal Domains of Plasmodium falciparum Variant Surface Antigen 2-Chondroitin Sulfate A (VAR2CSA) Inhibit Binding of CSA-Adherent Parasites to Placental Tissue
| Autor: | Tracy Saveria, Patrick E. Duffy, Andrew V. Oleinikov, Richa Chaturvedi, Joe Lograsso, Michal Fried, Gladys J. Keitany, Kathryn Wiliamson |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Placenta Recombinant Fusion Proteins Plasmodium falciparum Immunology Antibodies Protozoan Gene Expression Antigens Protozoan Syncytiotrophoblasts medicine.disease_cause Microbiology Antigen Pregnancy parasitic diseases Malaria Vaccines Cell Adhesion Escherichia coli medicine Animals Humans Antiserum Vaccines Synthetic biology Chondroitin Sulfates Infant Newborn biology.organism_classification Molecular biology Transmembrane protein Malaria Protein Structure Tertiary Rats Infectious Diseases medicine.anatomical_structure Microbial Immunity and Vaccines biology.protein Female Parasitology Antibody |
| Zdroj: | Infection and Immunity. 81:1031-1039 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.00978-12 |
| Popis: | Placental malaria (PM) is characterized by infected erythrocytes (IEs) that selectively bind to chondroitin sulfate A (CSA) and sequester in placental tissue. Variant surface antigen 2-CSA (VAR2CSA), a Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) protein family member, is expressed on the surface of placental IEs and mediates adherence to CSA on the surface of syncytiotrophoblasts. This transmembrane protein contains 6 Duffy binding-like (DBL) domains which might contribute to the specific adhesive properties of IEs. Here, we use laboratory isolate 3D7 VAR2CSA DBL domains expressed in Escherichia coli to generate antibodies specific for this protein. Flow cytometry results showed that antibodies generated against DBL4ε, DBL5ε, DBL6ε, and tandem double domains of DBL4-DBL5 and DBL5-DBL6 all bind to placental parasite isolates and to lab strains selected for CSA binding but do not bind to children's parasites. Antisera to DBL4ε and to DBL5ε inhibit maternal IE binding to placental tissue in a manner comparable to that for plasma collected from multigravid women. These antibodies also inhibit binding to CSA of several field isolates derived from pregnant women, while antibodies to double domains do not enhance the functional immune response. These data support DBL4ε and DBL5ε as vaccine candidates for pregnancy malaria and demonstrate that E. coli is a feasible tool for the large-scale manufacture of a vaccine based on these VAR2CSA domains. |
| Databáze: | OpenAIRE |
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