title: A plant-produced Pfs230 vaccine candidate blocks transmission of Plasmodium falciparum.
abstract: Plasmodium falciparum is transmitted to a new host after completing its sexual cycle within a mosquito. Developing vaccines against the parasite sexual stages is a critical component in the fight against malaria. We are targeting multiple proteins of P. falciparum which are found only on the surfaces of the sexual forms of the parasite and where antibodies against these proteins have been shown to block the progression of the parasite's life cycle in the mosquito and thus block transmission to the next human host. We have successfully produced a region of the Pfs230 antigen in our plant-based transient-expression system and evaluated this vaccine candidate in an animal model. This plant-produced protein, 230CMB, is expressed at approximately 800 mg/kg in fresh whole leaf tissue and is 100% soluble. Administration of 230CMB with >90% purity induces strong immune responses in rabbits with high titers of transmission-blocking antibodies, resulting in a greater than 99% reduction in oocyst counts in the presence of complement, as determined by a standard membrane feeding assay. Our data provide a clear perspective on the clinical development of a Pfs230-based transmission-blocking malaria vaccine.
authors.affiliation: Fraunhofer USA Center for Molecular Biotechnology, 9 Innovation Way, Suite 200, Newark, DE 19711, USA.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Farrance
authors.forename: Amy
authors.initials: A
authors.lastname: Rhee
authors.forename: R Mark
authors.initials: RM
authors.lastname: Jones
authors.forename: Konstantin
authors.initials: K
authors.lastname: Musiychuk
authors.forename: Moneim
authors.initials: M
authors.lastname: Shamloul
authors.forename: Satish
authors.initials: S
authors.lastname: Sharma
authors.forename: Vadim
authors.initials: V
authors.lastname: Mett
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Chichester
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Streatfield
authors.forename: Will
authors.initials: W
authors.lastname: Roeffen
authors.forename: Marga
authors.initials: M
authors.lastname: van de Vegte-Bolmer
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.forename: Takafumi
authors.initials: T
authors.lastname: Tsuboi
authors.forename: Olga V
authors.initials: OV
authors.lastname: Muratova
authors.forename: Yimin
authors.initials: Y
authors.lastname: Wu
authors.forename: Vidadi
authors.initials: V
authors.lastname: Yusibov
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology; D000953:Antigens, Protozoan / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology*; D006801:Humans; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control* / Q000635:transmission*; D010944:Plants; D030821:Plants, Genetically Modified / Q000235:genetics*; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D017780:Malaria Vaccines; C430263:Pfs230 antigen, Plasmodium falciparum; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D003165:Complement System Proteins