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  A high-affinity antibody against the CSP N-terminal domain lacks Plasmodium falciparum inhibitory activity

Thai, E., Costa, G., Weyrich, A., Murugan, R., Oyen, D., Prieto, K., et al. (2020). A high-affinity antibody against the CSP N-terminal domain lacks Plasmodium falciparum inhibitory activity. Journal of Experimental Medicine, 217(11): e20200061. doi:10.1084/jem.20200061.

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 Creators:
Thai, Elaine, Author
Costa, Giulia, Author
Weyrich, Anna, Author
Murugan, Rajagopal, Author
Oyen, David, Author
Prieto, Katherine, Author
Bosch, Alexandre, Author
Valleriani, Angelo1, Author              
Wu, Nicholas C., Author
Pholcharee, Tossapol, Author
Scally, Stephen W., Author
Wilson, Ian A., Author
Wardemann, Hedda, Author
Julien, Jean-Philippe, Author
Levashina, Elena A., Author
Affiliations:
1Angelo Valleriani, Theorie & Bio-Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863324              

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 Abstract: Malaria is a global health concern and research efforts are ongoing to develop a superior vaccine to RTS,S/AS01. To guide immunogen design, we seek a comprehensive understanding of the protective humoral response against Plasmodium falciparum circumsporozoite protein (PfCSP). In contrast to the well-studied responses to the repeat region and the C-terminus, the antibody response against the N-terminal domain of PfCSP (N-CSP) remains obscure. Here, we characterized the molecular recognition and functional efficacy of the N-CSP-specific monoclonal antibody 5D5. The crystal structure at 1.85 Åresolution revealed that 5D5 binds an α-helical epitope in N-CSP with high affinity through extensive shape and charge complementarity, and the unusual utilization of an N-linked glycan. Nevertheless, functional studies indicated low 5D5 binding to live Pf sporozoites, and lack of sporozoite inhibition in vitro and in mosquitoes. Overall, our data on low recognition and inhibition of sporozoites do not support the inclusion of the 5D5 epitope into the next generation of CSP-based vaccines.Summary Statement The Plasmodium falciparum sporozoite surface protein, PfCSP, is an attractive vaccine target, but the antibody response against the CSP N-terminal domain has remained understudied. Here, to guide immunogen design, Thai et al. provide insights into the binding motif and functional efficacy of the N-terminal domain-specific monoclonal antibody, 5D5.

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Language(s): eng - English
 Dates: 2020-01-142020
 Publication Status: Published in print
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 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1084/jem.20200061
BibTex Citekey: Thai2020.01.13.904425
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Title: Journal of Experimental Medicine
Source Genre: Journal
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Publ. Info: Baltimore, Md. : Rockefeller Institute for Medical Research
Pages: - Volume / Issue: 217 (11) Sequence Number: e20200061 Start / End Page: - Identifier: ISSN: 0022-1007