Induction of Plasmodium falciparum sporozoite-neutralizing antibodies upon vaccination with recombinant Pfsl6 vaccinia virus and/or recombinant Pfsl6 protein produced in yeast

Pfsl6 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 Pfsl6 and to investigate its role during transmission and hepatocyte invasion, immunization experiments were performed with both a Pfs 16-specific recombinant vaccinia virus and virus-like particles produced in yeast composed of the hepatitis B surface antigen (HBsAg) and antigen Pfs 16 fused to HBsAg. Upon transformation of yeast cells, harbouring a genomic copy of the HBsAg gene, with a plasmid carrying the fusion gene Pfsl6 -HBsAg (Pfsl6 -S) virus-like hybrid particles composed of HBsAg and Pfsló-S were formed of a size similar to those present in human sera after infection with the hepatitis B virus. Cells infected with recombinant Pfsl6 vaccinia virus synthesized a polypeptide of approx. 16 kDa that reacted with a Pfs 16-specific polyclonal antibody. Animals vaccinated with the yeast hybrid particles and/or recombinant vaccinia virus both produced Pfsl6 -specific Abbreviations: CS protein, circumsporozoite protein; GWB, gamétocyte Western blot analysis; ELISA, Enzyme-linked im­ munosorbent assay; HBsAg, hepatitis B surface antigen; IFA, indirect immunofluorescence assay; ISI, inhibition of sporozoite invasion; Pfsl6-S, Pfsl6-HBsAg fusion protein; Pfsl6-S,S, virus­ like particles composed of HBsAg and Pfsl6-S; SIFA, suspension indirect immunofluorescence assay; SWB, sporozoite Western blot analysis; TB assay, transmission-blocking assay. 1 Present address: Department of Parasitology, Janssen Pharmaceulica, Turnhoutseweg 30, 2340 Beerse, Belgium. n _ Note: This publication is dedicated to the late John Schoen­ makers. * Corresponding author. Tel: (31-80) 652-911; Fax: (31-80) 652-938. 0166~6851/95/$09.50 © 1995 Elsevier Science B.V. All rights reserved SSDI 0 1 6 6 -6 8 5 1 (9 5 )0 0 0 7 2 -0 180 I.LM.D. Moelans et al / Molecular and Biochemical Parasitology 72 (1995) 179-192 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.