Epitope Analysis of the Malaria Surface Antigen Pfs48/45 Identifies a Subdomain That Elicits Transmission Blocking Antibodies

Outchkourov, Nikolay, Vermunt, Adriaan, Jansen, Josephine, Kaan, Anita, Roeffen, Will, Teelen, Karina, Lasonder, Edwin, Braks, Anneke, van de Vegte-Bolmer, Marga, Qiu, Li Yan, Sauerwein, Robert and Stunnenberg, Hendrik G. (2007) Epitope Analysis of the Malaria Surface Antigen Pfs48/45 Identifies a Subdomain That Elicits Transmission Blocking Antibodies. Journal of Biological Chemistry, 282 (23). pp. 17148-17156. ISSN 0021-9258

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Official URL: https://doi.org/10.1074/jbc.M700948200


Pfs48/45, a member of a Plasmodium-specific protein family, displays conformation-dependent epitopes and is an important target for malaria transmission-blocking (TB) immunity. To design a recombinant Pfs48/45-based TB vaccine, we analyzed the conformational TB epitopes of Pfs48/45. The Pfs48/45 protein was found to consist of a C-terminal six-cysteine module recognized by anti-epitope I antibodies, a middle four-cysteine module recognized by anti-epitopes IIb and III, and an N-terminal module recognized by anti-epitope V antibodies. Refolding assays identified that a fragment of 10 cysteines (10C), comprising the middle four-cysteine and the C-terminal six-cysteine modules, possesses superior refolding capacity. The refolded and partially purified 10C conformer elicited antibodies in mice that targeted at least two of the TB epitopes (I and III). The induced antibodies could block the fertilization of Plasmodium falciparum gametes in vivo in a concentration-dependent manner. Our results provide important insight into the structural organization of the Pfs48/45 protein and experimental support for a Pfs48/45-based subunit vaccine.

Item Type: Article
Additional Information: Funding information: This study was financially supported by European Malaria Vaccine Initiative Grant 041222 and by EuroMalvac II Contract QLK2-CT-2002-01197. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Subjects: C700 Molecular Biology, Biophysics and Biochemistry
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Elena Carlaw
Date Deposited: 04 Jun 2021 09:16
Last Modified: 31 Jul 2021 11:06
URI: http://nrl.northumbria.ac.uk/id/eprint/46346

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