Functional human IgA targets a conserved site on malaria sporozoites
| العنوان: | Functional human IgA targets a conserved site on malaria sporozoites |
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| المؤلفون: | Kassoum Kayentao, Joseph R. Francica, Carolina Barillas-Mury, Aissata Ongoiba, Rachel Vistein, T. Pholcharee, Photini Sinnis, Shanping Li, Safiatou Doumbo, Hyeseon Cho, Boubacar Traore, Barbara J. Flynn, Peter D. Crompton, Ming Zhao, Alison Roth, Lawrence Wang, Robert A. Seder, Mary E. Peterson, Lisa R. Olano, Lais Pereira, David Oyen, Azza H. Idris, Marlon Dillon, Ian A. Wilson, Patricia J. Lee, Samantha O. Aylor, Alvaro Molina-Cruz, Jeff Skinner, Sachie Kanatani, Arne Schön, Didier Doumtabe, Joshua Tan |
| المصدر: | Science translational medicine |
| بيانات النشر: | American Association for the Advancement of Science (AAAS), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Plasmodium falciparum, Protozoan Proteins, Antibodies, Protozoan, Target peptide, Article, Epitope, Mice, Immunity, parasitic diseases, medicine, Animals, Humans, biology, General Medicine, biology.organism_classification, medicine.disease, Isotype, Virology, Immunoglobulin A, Malaria, Circumsporozoite protein, Sporozoites, biology.protein, Antibody |
| الوصف: | Immunoglobulin (Ig)A antibodies play a critical role in protection against mucosal pathogens. However, the role of serum IgA in immunity to non-mucosal pathogens, such as Plasmodium falciparum, is poorly characterized, despite being the second most abundant isotype in blood after IgG. Here, we investigated the circulating IgA response in humans to Plasmodium falciparum sporozoites that are injected into the skin by mosquitoes and migrate to the liver via the bloodstream to initiate malaria infection. We found that circulating IgA was induced in three independent sporozoite-exposed cohorts: individuals living in an endemic region in Mali, malaria-naïve individuals immunized intravenously with three large doses of irradiated sporozoites, and malaria-naïve individuals exposed to a single controlled mosquito bite infection. Mechanistically, we found evidence in an animal model that IgA responses were induced by sporozoites at dermal inoculation sites. From malaria-resistant individuals, we isolated several IgA monoclonal antibodies that reduced liver parasite burden in mice. One antibody, MAD2-6, bound to a conserved epitope in the N-terminus of the P. falciparum circumsporozoite protein, the dominant protein on the sporozoite surface. Crystal structures of this antibody revealed a unique mode of binding whereby two Fabs simultaneously bound either side of the target peptide. This study reveals a role for circulating IgA in malaria and identifies the N-terminus of the circumsporozoite protein as a target of functional antibodies. |
| تدمد: | 1946-6242 1946-6234 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8556a9825d193b988d58bba913deb13b https://doi.org/10.1126/scitranslmed.abg2344 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8556a9825d193b988d58bba913deb13b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19466242 19466234 |
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