TY - JOUR
T1 - Epitope analysis of the malaria surface antigen Pfs48/45 identifies a subdomain that elicits transmission blocking antibodies
AU - Outchkourov, Nikolay
AU - Vermunt, Adriaan
AU - Jansen, Josephine
AU - Kaan, Anita
AU - Roeffen, Will
AU - Teelen, Karina
AU - Lasonder, Edwin
AU - Braks, Anneke
AU - Van De Vegte-Bolmer, Marga
AU - Li, Yan Qiu
AU - Sauerwein, Robert
AU - Stunnenberg, Hendrik G.
PY - 2007/6/8
Y1 - 2007/6/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34447118848&partnerID=8YFLogxK
U2 - 10.1074/jbc.M700948200
DO - 10.1074/jbc.M700948200
M3 - Article
C2 - 17426022
AN - SCOPUS:34447118848
SN - 0021-9258
VL - 282
SP - 17148
EP - 17156
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 23
ER -