title: A novel plant-produced Pfs25 fusion subunit vaccine induces long-lasting transmission blocking antibody responses.
abstract: Malaria transmission blocking vaccines (TBV) directed against proteins expressed on sexual stages of Plasmodium falciparum in the mosquito midgut are considered an effective means to reduce malaria transmission. Antibodies induced by TBV block sporogonic development in the mosquito, and thus transmission to the next human host. The Pfs25 protein, expressed on the surface of gametes, zygotes and ookinetes, is one of the primary targets for TBV development. Using a plant virus-based transient expression system, we have successfully produced Pfs25 fused to a modified lichenase (LicKM) carrier in Nicotiana benthamiana, purified and characterized the protein (Pfs25-FhCMB), and evaluated this vaccine candidate in animal models for the induction of transmission blocking antibodies. Soluble Pfs25-FhCMB was expressed in plants at a high level, and induced transmission blocking antibodies that persisted for up to 6 months post immunization in mice and rabbits. These data demonstrate the potential of the new malaria vaccine candidate and also support feasibility of expressing Plasmodium antigens in a plant-based system.
authors.affiliation: a Fraunhofer USA Center for Molecular Biotechnology; Newark, DE USA.
authors.forename: R Mark
authors.initials: RM
authors.lastname: Jones
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Chichester
authors.forename: Slobodanka
authors.initials: S
authors.lastname: Manceva
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Gibbs
authors.forename: Konstantin
authors.initials: K
authors.lastname: Musiychuk
authors.forename: Moneim
authors.initials: M
authors.lastname: Shamloul
authors.forename: Joey
authors.initials: J
authors.lastname: Norikane
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Streatfield
authors.forename: Marga
authors.initials: M
authors.lastname: van de Vegte-Bolmer
authors.forename: Will
authors.initials: W
authors.lastname: Roeffen
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.forename: Vidadi
authors.initials: V
authors.lastname: Yusibov
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors; D006026:Glycoside Hydrolases / Q000235:genetics / Q000378:metabolism; D008288:Malaria / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D008807:Mice, Inbred BALB C; D030821:Plants, Genetically Modified / Q000235:genetics / Q000378:metabolism; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology; D017800:Potyvirus / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013997:Time Factors; D014026:Nicotiana / Q000235:genetics / Q000378:metabolism; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D002352:Carrier Proteins; D017780:Malaria Vaccines; C071284:Pfs25 protein, Plasmodium falciparum; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D006026:Glycoside Hydrolases; C028020:licheninase
keywords: Pfs25; Plasmodium falciparum; fusion protein; lichenase; malaria; plant-produced antigen; subunit vaccine; transmission blocking vaccine