Recombinant human antibodies specific for the Pfs48/45 protein of the malaria parasite Plasmodium falciparum.
We report the first construction of two combinatorial human phage display libraries derived from malaria-immune patients. Specific single-chain Fv fragments (scFv) against Pfs48/45, a gamete surface protein of the sexual stages of Plasmodium falciparum, were selected and analyzed extensively. The selected scFv reacted with the surface of extracellular sexual forms of the parasite and showed Pfs48/45 reactivity on immunoblot. The scFv inhibit binding of human malaria sera to native Pfs48/45 from gametocytes. Moreover, the scFv bind to target epitopes of Pfs48/45 exposed in natural infections. Sequence analysis of eight scFv clones specific for epitope III of Pfs48/45 revealed that these clones could be divided into one V(H) family-derived germ-line gene (V(H)1) and two V(L) family segments (V(L)2 and V(K)I).
Department of Medical Microbiology, University Medical Center St. Radboud, 6500 HB Nijmegen, The Netherlands. roeffen@mmb.azn.nl
W F
WF
Roeffen
J M
JM
Raats
K
K
Teelen
R M
RM
Hoet
W M
WM
Eling
W J
WJ
van Venrooij
R W
RW
Sauerwein
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D001435:Bacteriophages / Q000235:genetics; D000939:Epitopes / Q000276:immunology; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000276:immunology*; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D017386:Sequence Homology, Amino Acid
D000906:Antibodies; D000939:Epitopes; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C084847:pfs48-45 protein, Plasmodium falciparum