Natural Parasite Exposure Induces Protective Human Anti-Malarial Antibodies
| العنوان: | Natural Parasite Exposure Induces Protective Human Anti-Malarial Antibodies |
|---|---|
| المؤلفون: | Eric Marois, Elena A. Levashina, Giulia Costa, Shahid M. Khan, Brandon K. Sack, G. Triller, Jean-Philippe Julien, Ayola A. Adegnika, Chris J. Janse, A. Bosch, S.W. Scally, Ahmed M. Salman, Benjamin Mordmüller, Stefan H. I. Kappe, Rajagopal Murugan, Maria Pissarev, Cornelia Kreschel, Hedda Wardemann |
| المصدر: | Immunity Immunity, 47(6), 1197 |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Models, Molecular, Protein Conformation, alpha-Helical, Plasmodium berghei, Immunology, Plasmodium falciparum, Protozoan Proteins, Antibodies, Protozoan, Gene Expression, Antigens, Protozoan, Complementarity determining region, Crystallography, X-Ray, Epitope, Article, Affinity maturation, 03 medical and health sciences, Epitopes, Mice, 0302 clinical medicine, Antigen, parasitic diseases, Immunology and Allergy, Animals, Humans, Protein Interaction Domains and Motifs, Malaria, Falciparum, B-Lymphocytes, biology, biology.organism_classification, Virology, Recombinant Proteins, 3. Good health, Immunity, Humoral, Malaria, Circumsporozoite protein, 030104 developmental biology, Infectious Diseases, Sporozoites, Humoral immunity, biology.protein, Female, Protein Conformation, beta-Strand, Antibody, Immunoglobulin Heavy Chains, Immunologic Memory, 030217 neurology & neurosurgery, Protein Binding |
| الوصف: | Antibodies against the NANP repeat of circumsporozoite protein (CSP), the major surface antigen of Plasmodium falciparum (Pf) sporozoites, can protect from malaria in animal models but protective humoral immunity is difficult to induce in humans. Here we cloned and characterized rare affinity-matured human NANP-reactive memory B cell antibodies elicited by natural Pf exposure that potently inhibited parasite transmission and development in vivo. We unveiled the molecular details of antibody binding to two distinct protective epitopes within the NANP repeat. NANP repeat recognition was largely mediated by germline encoded and immunoglobulin (Ig) heavy-chain complementarity determining region 3 (HCDR3) residues, whereas affinity maturation contributed predominantly to stabilizing the antigen-binding site conformation. Combined, our findings illustrate the power of exploring human anti-CSP antibody responses to develop tools for malaria control in the mammalian and the mosquito vector and provide a molecular basis for the structure-based design of next-generation CSP malaria vaccines. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::85652cb81df8d8f893edb4ec2ecec472 https://hdl.handle.net/1887/115822 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....85652cb81df8d8f893edb4ec2ecec472 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |