Induction of Plasmodium falciparum sporozoite-neutralizing antibodies upon vaccination with recombinant Pfs16 vaccinia virus and/or recombinant Pfs16 protein produced in yeast.
Pfs16 is a sexual stage/sporozoite-specific antigen of Plasmodium falciparum and is a potential candidate for a sporozoite-neutralizing vaccine. To obtain more information on the function of Pfs16 and to investigate its role during transmission and hepatocyte invasion, immunization experiments were performed with both a Pfs16-specific recombinant vaccinia virus and virus-like particles produced in yeast composed of the hepatitis B surface antigen (HBsAg) and antigen Pfs16 fused to HBsAg. Upon transformation of yeast cells, harbouring a genomic copy of the HBsAg gene, with a plasmid carrying the fusion gene Pfs16-HBsAg (Pfs16-S) virus-like hybrid particles composed of HBsAg and Pfs16-S were formed of a size similar to those present in human sera after infection with the hepatitis B virus. Cells infected with recombinant Pfs16 vaccinia virus synthesized a polypeptide of approx. 16 kDa that reacted with a Pfs16-specific polyclonal antibody. Animals vaccinated with the yeast hybrid particles and/or recombinant vaccinia virus both produced Pfs16-specific antibodies. These antibodies showed no transmission-blocking activity, but they efficiently diminished or abolished in vitro invasion of sporozoites into human hepatoma cells (HepG2-A16) and primary human hepatocytes.
Department of Molecular Biology, Faculty of Science, University of Nijmegen, The Netherlands.
I I
II
Moelans
J
J
Cohen
M
M
Marchand
C
C
Molitor
P
P
de Wilde
J F
JF
van Pelt
M R
MR
Hollingdale
W F
WF
Roeffen
W M
WM
Eling
C T
CT
Atkinson
D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000469:parasitology; D000913:Antibodies, Protozoan / Q000096:biosynthesis* / Q000276:immunology; D000918:Antibody Specificity; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007303:Insect Vectors / Q000469:parasitology; D008099:Liver / Q000166:cytology; D008113:Liver Neoplasms / Q000473:pathology; D017780:Malaria Vaccines / Q000276:immunology*; D008565:Membrane Proteins / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014614:Vaccines, Synthetic / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics*
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D006514:Hepatitis B Surface Antigens; D017780:Malaria Vaccines; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; C068959:Pfs16 protein, Plasmodium falciparum