title: Transmission blocking potency and immunogenicity of a plant-produced Pvs25-based subunit vaccine against Plasmodium vivax.
abstract: Malaria transmission blocking (TB) vaccines (TBVs) directed against proteins expressed on the sexual stages of Plasmodium parasites are a potentially effective means to reduce transmission. Antibodies induced by TBVs block parasite development in the mosquito, and thus inhibit transmission to further human hosts. The ookinete surface protein P25 is a primary target for TBV development. Recently, transient expression in plants using hybrid viral vectors has demonstrated potential as a strategy for cost-effective and scalable production of recombinant vaccines. Using a plant virus-based expression system, we produced recombinant P25 protein of Plasmodium vivax (Pvs25) in Nicotiana benthamiana fused to a modified lichenase carrier protein. This candidate vaccine, Pvs25-FhCMB, was purified, characterized and evaluated for immunogenicity and efficacy using multiple adjuvants in a transgenic rodent model. An in vivo TB effect of up to a 65% reduction in intensity and 54% reduction in prevalence was observed using Abisco-100 adjuvant. The ability of this immunogen to induce a TB response was additionally combined with heterologous prime-boost vaccination with viral vectors expressing Pvs25. Significant blockade was observed when combining both platforms, achieving a 74% and 68% reduction in intensity and prevalence, respectively. This observation was confirmed by direct membrane feeding on field P. vivax samples, resulting in reductions in intensity/prevalence of 85.3% and 25.5%. These data demonstrate the potential of this vaccine candidate and support the feasibility of expressing Plasmodium antigens in a plant-based system for the production of TBVs, while demonstrating the potential advantages of combining multiple vaccine delivery systems to maximize efficacy.
authors.affiliation: Department of Life Sciences, Sir Alexander Fleming Building, Imperial College London, Imperial College Road, South Kensington, London SW7 2AZ, UK. Electronic address: andrew.blagborough@imperial.ac.uk.
authors.forename: A M
authors.initials: AM
authors.lastname: Blagborough
authors.affiliation: Fraunhofer USA Center for Molecular Biotechnology, Newark, DE, USA.
authors.forename: K
authors.initials: K
authors.lastname: Musiychuk
authors.affiliation: Fraunhofer USA Center for Molecular Biotechnology, Newark, DE, USA.
authors.forename: H
authors.initials: H
authors.lastname: Bi
authors.affiliation: Fraunhofer USA Center for Molecular Biotechnology, Newark, DE, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Jones
authors.affiliation: Fraunhofer USA Center for Molecular Biotechnology, Newark, DE, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Chichester
authors.affiliation: Fraunhofer USA Center for Molecular Biotechnology, Newark, DE, USA.
authors.forename: S
authors.initials: S
authors.lastname: Streatfield
authors.affiliation: Department of Life Sciences, Sir Alexander Fleming Building, Imperial College London, Imperial College Road, South Kensington, London SW7 2AZ, UK.
authors.forename: K A
authors.initials: KA
authors.lastname: Sala
authors.affiliation: Department of Life Sciences, Sir Alexander Fleming Building, Imperial College London, Imperial College Road, South Kensington, London SW7 2AZ, UK.
authors.forename: S E
authors.initials: SE
authors.lastname: Zakutansky
authors.affiliation: Department of Life Sciences, Sir Alexander Fleming Building, Imperial College London, Imperial College Road, South Kensington, London SW7 2AZ, UK.
authors.forename: L M
authors.initials: LM
authors.lastname: Upton
authors.affiliation: Jenner Institute, The University of Oxford, Roosevelt Road, Oxford OX9 2PP, UK.
authors.forename: R E
authors.initials: RE
authors.lastname: Sinden
authors.affiliation: Jenner Institute, The University of Oxford, Roosevelt Road, Oxford OX9 2PP, UK.
authors.forename: I
authors.initials: I
authors.lastname: Brian
authors.affiliation: Jenner Institute, The University of Oxford, Roosevelt Road, Oxford OX9 2PP, UK.
authors.forename: S
authors.initials: S
authors.lastname: Biswas
authors.affiliation: Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand.
authors.forename: J
authors.initials: J
authors.lastname: Sattabonkot
authors.affiliation: Fraunhofer USA Center for Molecular Biotechnology, Newark, DE, USA.
authors.forename: V
authors.initials: V
authors.lastname: Yusibov
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000090266:Chromobox Protein Homolog 5; D005260:Female; D007117:Immunization, Secondary; D017780:Malaria Vaccines / Q000276:immunology*; D016780:Malaria, Vivax / Q000517:prevention & control*; D008807:Mice, Inbred BALB C; D030821:Plants, Genetically Modified; D010966:Plasmodium vivax; D015800:Protozoan Proteins / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D014026:Nicotiana; D022223:Vaccines, Subunit / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; C000715594:CBX5 protein, human; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D000090266:Chromobox Protein Homolog 5
keywords: Malaria; Plant-produced antigen; Plasmodium; Pvs25; Subunit vaccine; Transmission blocking vaccine