| Title: |
Target-agnostic identification of human antibodies to Plasmodium falciparum sexual forms reveals cross stage recognition of glutamate-rich repeats |
| Authors: |
Amen, Axelle; Yoo, Randy; Fabra-García, Amanda; Bolscher, Judith; Stone, William J. R.; Bally, Isabelle; Dergan-Dylon, Sebastián; Kucharska, Iga; de Jong, Roos; de Bruijni, Marloes; Bousema, Teun; Richter King, C.; Macgill, Randall; Sauerwein, Robert; Julien, Jean-Philippe; Jore, Matthijs; Poignard, Pascal |
| Contributors: |
Institut de biologie structurale (IBS - UMR 5075); Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG); Direction de Recherche Fondamentale (CEA) (DRF (CEA)); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA); University of Toronto; Radboud University Medical Center Nijmegen (RadboudUMC); London School of Hygiene and Tropical Medicine (LSHTM); The Hospital for sick children Toronto (SickKids); Department of Biochemistry University of Toronto; Medical Microbiology; Grenoble Instruct-ERIC center (ISBG; UAR 3518 CNRS-CEA-UGA-EMBL) |
| Source: |
EISSN: 2050-084X ; eLife ; https://hal.science/hal-04717738 ; eLife, 2024, 13, pp.1-28. ⟨10.7554/eLife.97865.2⟩ |
| Publisher Information: |
CCSD; eLife Sciences Publication |
| Publication Year: |
2024 |
| Collection: |
Université Grenoble Alpes: HAL |
| Subject Terms: |
[SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology; [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology; [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology |
| Description: |
International audience ; t Circulating sexual stages of Plasmodium falciparum (Pf) can be transmitted from humans to mosquitoes, thereby furthering the spread of malaria in the population. It is well established that antibodies (Abs) can efficiently block parasite transmission. In search for naturally acquired Ab targets on sexual stages, we established an efficient method for target-agnostic single B cell activation followed by high-throughput selection of human monoclonal antibodies (mAbs) reactive to sexual stages of Pf in the form of gamete and gametocyte extract. We isolated mAbs reactive against a range of Pf proteins including well-established targets Pfs48/45 and Pfs230. One mAb, B1E11K, was cross-reactive to various proteins containing glutamate-rich repetitive elements expressed at different stages of the parasite life cycle. A crystal structure of two B1E11K Fab domains in complex with its main antigen, RESA, expressed on asexual blood stages, showed binding of B1E11K to a repeating epitope motif in a head-to-head conformation engaging in affinity-matured homotypic interactions. Thus, this mode of recognition of Pf proteins, previously described only for PfCSP, extends to other repeats expressed across various stages. The findings augment our understanding of immune-pathogen interactions to repeating elements of the Plasmodium parasite proteome and underscore the potential of the novel mAb identification method used to provide new insights into the natural humoral immune response against Pf . Impact Statement A naturally acquired human monoclonal antibody recognizes proteins expressed at different stages of the Plasmodium falciparum lifecycle through affinity-matured homotypic interactions with glutamate-rich repeats |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/37961136; BIORXIV: 2023.11.03.565335; PUBMED: 37961136; PUBMEDCENTRAL: PMC10635103 |
| DOI: |
10.7554/eLife.97865.2 |
| Availability: |
https://hal.science/hal-04717738; https://hal.science/hal-04717738v1/document; https://hal.science/hal-04717738v1/file/Amen%20et%20al.%202024.pdf; https://doi.org/10.7554/eLife.97865.2 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.D52655C5 |
| Database: |
BASE |