title: A plant-produced Pfs25 VLP malaria vaccine candidate induces persistent transmission blocking antibodies against Plasmodium falciparum in immunized mice.
abstract: Malaria transmission blocking vaccines (TBVs) are considered an effective means to control and eventually eliminate malaria. The Pfs25 protein, expressed predominantly on the surface of the sexual and sporogonic stages of Plasmodium falciparum including gametes, zygotes and ookinetes, is one of the primary targets for TBV. It has been demonstrated that plants are an effective, highly scalable system for the production of recombinant proteins, including virus-like particles (VLPs). We engineered VLPs (Pfs25-CP VLP) comprising Pfs25 fused to the Alfalfa mosaic virus coat protein (CP) and produced these non-enveloped hybrid VLPs in Nicotiana benthamiana plants using a Tobacco mosaic virus-based 'launch' vector. Purified Pfs25-CP VLPs were highly consistent in size (19.3±2.4 nm in diameter) with an estimated 20-30% incorporation of Pfs25 onto the VLP surface. Immunization of mice with one or two doses of Pfs25-CP VLPs plus Alhydrogel® induced serum antibodies with complete transmission blocking activity through the 6 month study period. These results support the evaluation of Pfs25-CP VLP as a potential TBV candidate and the feasibility of the 'launch' vector technology for the production of VLP-based recombinant vaccines against infectious diseases.
authors.affiliation: Fraunhofer USA Center for Molecular Biotechnology, Newark, Delaware, United States of America.
authors.forename: R Mark
authors.initials: RM
authors.lastname: Jones
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Chichester
authors.forename: Vadim
authors.initials: V
authors.lastname: Mett
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jaje
authors.forename: Stephen
authors.initials: S
authors.lastname: Tottey
authors.forename: Slobodanka
authors.initials: S
authors.lastname: Manceva
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Casta
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: Valentina
authors.initials: V
authors.lastname: Mett
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; D019138:Antibodies, Blocking / Q000276:immunology*; D000953:Antigens, Protozoan / Q000276:immunology; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology; D011994:Recombinant Proteins
chemical_list: D019138:Antibodies, Blocking; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011994:Recombinant Proteins