Epitope analysis of the malaria surface antigen pfs48/45 identifies a subdomain that elicits transmission blocking antibodies.
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.
Outchkourov
Nikolay
N
Department of Molecular Biology, NCMLS, Radboud University Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Vermunt
Adriaan
A
Jansen
Josephine
J
Kaan
Anita
A
Roeffen
Will
W
Teelen
Karina
K
Lasonder
Edwin
E
Braks
Anneke
A
van de Vegte-Bolmer
Marga
M
Qiu
Li Yan
LY
Sauerwein
Robert
R
Stunnenberg
Hendrik G
HG
D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis*; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D015800:Protozoan Proteins / Q000276:immunology*; D017386:Sequence Homology, Amino Acid
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000939:Epitopes; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; C084847:pfs48-45 protein, Plasmodium falciparum