Rare PfCSP C-terminal antibodies induced by live sporozoite vaccination are ineffective against malaria infection
| العنوان: | Rare PfCSP C-terminal antibodies induced by live sporozoite vaccination are ineffective against malaria infection |
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| المؤلفون: | Peter G. Kremsner, Stephen L. Hoffman, G. Triller, S.W. Scally, B. Kim Lee Sim, A. Bosch, Hedda Wardemann, Jean-Philippe Julien, Elena A. Levashina, Giulia Costa, Benjamin Mordmüller, Rajagopal Murugan |
| المصدر: | Journal of Experimental Medicine The Journal of Experimental Medicine |
| بيانات النشر: | Rockefeller University Press, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Models, Molecular, 0301 basic medicine, Cellular immunity, Protein Conformation, medicine.drug_class, Plasmodium falciparum, 030231 tropical medicine, Immunology, Protozoan Proteins, Antibodies, Protozoan, Epitopes, T-Lymphocyte, Biology, Monoclonal antibody, Epitope, Epitopes, 03 medical and health sciences, 0302 clinical medicine, Protein Domains, Malaria Vaccines, parasitic diseases, medicine, Immunology and Allergy, Plasmodium berghei, Amino Acid Sequence, Malaria, Falciparum, Research Articles, Vaccination, Brief Definitive Report, biology.organism_classification, Virology, Recombinant Proteins, 3. Good health, Circumsporozoite protein, 030104 developmental biology, Immunization, biology.protein, Antibody |
| الوصف: | Scally et al. show the molecular, structural, and functional characterization of human antibodies against the C-terminal domain of Plasmodium falciparum (Pf) circumsporozoite (CSP [C-PfCSP]) and reveal that its arrangement on the Pf sporozoite surface and epitope polymorphism contribute to poor C-PfCSP immunogenicity and ineffective humoral responses in volunteers protected against Pf malaria. Antibodies against the central repeat of the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) inhibit parasite activity and correlate with protection from malaria. However, the humoral response to the PfCSP C terminus (C-PfCSP) is less well characterized. Here, we describe B cell responses to C-PfCSP from European donors who underwent immunization with live Pf sporozoites (PfSPZ Challenge) under chloroquine prophylaxis (PfSPZ-CVac), and were protected against controlled human malaria infection. Out of 215 PfCSP-reactive monoclonal antibodies, only two unique antibodies were specific for C-PfCSP, highlighting the rare occurrence of C-PfCSP–reactive B cells in PfSPZ-CVac–induced protective immunity. These two antibodies showed poor sporozoite binding and weak inhibition of parasite traversal and development, and did not protect mice from infection with PfCSP transgenic Plasmodium berghei sporozoites. Structural analyses demonstrated that one antibody interacts with a polymorphic region overlapping two T cell epitopes, suggesting that variability in C-PfCSP may benefit parasite escape from humoral and cellular immunity. Our data identify important features underlying C-PfCSP shortcomings as a vaccine target. |
| وصف الملف: | application/pdf |
| تدمد: | 1540-9538 0022-1007 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::28c64b2fe287a5029be796438b048846 https://doi.org/10.1084/jem.20170869 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....28c64b2fe287a5029be796438b048846 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15409538 00221007 |
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