A Plasmodium falciparum 48/45 single epitope R0.6C subunit protein elicits high levels of transmission blocking antibodies.
The sexual stage Pfs48/45 antigen is a well-established lead candidate for a transmission blocking (TB) vaccine because of its critical role in parasite fertilization. We have recently produced the carboxy-terminal 10C-fragment of Pfs48/45 containing three known epitopes for TB antibodies as a chimera with the N-terminal region of GLURP (R0). The resulting fusion protein elicited high titer TB antibodies in rodents. To increase the relatively low yield of correctly folded Pfs48/45 we have generated a series of novel chimera truncating the 10C-fragments to 6 cysteine residues containing sub-units (6C). All constructs harbor the major epitope I for TB antibodies. One of these sub-units (R0.6Cc), produced high yields of correctly folded conformers, which could be purified by a simple 2-step procedure. Purified R0.6Cc was stable and elicits high titer TB antibodies in rats. The yield, purity and stability of R0.6Cc allows for further clinical development.
Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark; Centre for Medical Parasitology at Department of International Health, Immunology, and Microbiology, University of Copenhagen, and Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Susheel K
SK
Singh
Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
Will
W
Roeffen
Centre for Medical Parasitology at Department of International Health, Immunology, and Microbiology, University of Copenhagen, and Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Gorm
G
Andersen
Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Immunology & Infection, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Teun
T
Bousema
Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark.
Michael
M
Christiansen
Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
Robert
R
Sauerwein
Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark; Centre for Medical Parasitology at Department of International Health, Immunology, and Microbiology, University of Copenhagen, and Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. Electronic address: mth@ssi.dk.
Michael
M
Theisen
D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology*; D000913:Antibodies, Protozoan / Q000276:immunology*; D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression; D016778:Malaria, Falciparum / Q000517:prevention & control* / Q000635:transmission; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology
D019138:Antibodies, Blocking; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000939:Epitopes; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins
GLURP; Pfs48/45; Plasmodium falciparum; SMFA; Transmission blocking