A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein.

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Version: Author's accepted manuscript
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Serval ID
serval:BIB_DC5884589CC7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein.
Journal
Nature Medicine
Author(s)
Tan J., Sack B.K., Oyen D., Zenklusen I., Piccoli L., Barbieri S., Foglierini M., Fregni C.S., Marcandalli J., Jongo S., Abdulla S., Perez L., Corradin G., Varani L., Sallusto F., Sim BKL, Hoffman S.L., Kappe SHI, Daubenberger C., Wilson I.A., Lanzavecchia A.
ISSN
1546-170X (Electronic)
ISSN-L
1078-8956
Publication state
Published
Issued date
2018
Peer-reviewed
Oui
Volume
24
Number
4
Pages
401-407
Language
english
Abstract
Immunization with attenuated Plasmodium falciparum sporozoites (PfSPZs) has been shown to be protective against malaria, but the features of the antibody response induced by this treatment remain unclear. To investigate this response in detail, we isolated IgM and IgG monoclonal antibodies from Tanzanian volunteers who were immunized with repeated injection of Sanaria PfSPZ Vaccine and who were found to be protected from controlled human malaria infection with infectious homologous PfSPZs. All isolated IgG monoclonal antibodies bound to P. falciparum circumsporozoite protein (PfCSP) and recognized distinct epitopes in its N terminus, NANP-repeat region, and C terminus. Strikingly, the most effective antibodies, as determined in a humanized mouse model, bound not only to the repeat region, but also to a minimal peptide at the PfCSP N-terminal junction that is not in the RTS,S vaccine. These dual-specific antibodies were isolated from different donors and were encoded by VH3-30 or VH3-33 alleles that encode tryptophan or arginine at position 52. Using structural and mutational data, we describe the elements required for germline recognition and affinity maturation. Our study provides potent neutralizing antibodies and relevant information for lineage-targeted vaccine design and immunization strategies.
Pubmed
Web of science
Create date
22/03/2018 18:13
Last modification date
30/04/2021 6:15
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