title: Correctly folded Pfs48/45 protein of Plasmodium falciparum elicits malaria transmission-blocking immunity in mice.
abstract: Malaria kills >1 million people each year, in particular in sub-Saharan Africa. Although asexual forms are directly responsible for disease and death, sexual stages account for the transmission of Plasmodium parasites from human to the mosquito vector and therefore the spread of the parasite in the population. Development of a malaria vaccine is urgently needed to reduce morbidity and mortality. Vaccines against sexual stages of Plasmodium falciparum are meant to decrease the force of transmission and consequently reduce malaria burden. Pfs48/45 is specifically expressed in sexual stages and is a well established transmission-blocking (TB) vaccine candidate. However, production of correctly folded recombinant Pfs48/45 protein with display of its TB epitopes has been a major challenge. Here, we show the production of a properly folded Pfs48/45 C-terminal fragment by simultaneous coexpression with four periplasmic folding catalysts in Escherichia coli. This C-terminal fragment fused to maltose binding protein was produced at medium scale with >90% purity and a stability over at least a 9-month period. It induces uniform and high antibody titers in mice and elicits functional TB antibodies in standard membrane feeding assays in 90% of the immunized mice. Our data provide a clear perspective on the clinical development of a Pfs48/45-based TB malaria vaccine.
authors.affiliation: Departments of Molecular Biology and Medical Microbiology, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Nikolay S
authors.initials: NS
authors.lastname: Outchkourov
authors.forename: Will
authors.initials: W
authors.lastname: Roeffen
authors.forename: Anita
authors.initials: A
authors.lastname: Kaan
authors.forename: Josephine
authors.initials: J
authors.lastname: Jansen
authors.forename: Adrian
authors.initials: A
authors.lastname: Luty
authors.forename: Danielle
authors.initials: D
authors.lastname: Schuiffel
authors.forename: Geert Jan
authors.initials: GJ
authors.lastname: van Gemert
authors.forename: Marga
authors.initials: M
authors.lastname: van de Vegte-Bolmer
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Stunnenberg
mesh_terms: D000818:Animals; D002384:Catalysis; D005260:Female; D007125:Immunogenetics; D008288:Malaria / Q000276:immunology* / Q000469:parasitology / Q000635:transmission*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010963:Plasmodium falciparum / Q000276:immunology* / Q000378:metabolism*; D017510:Protein Folding; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; C084847:pfs48-45 protein, Plasmodium falciparum