title: The Plasmodium berghei sexual stage antigen PSOP12 induces anti-malarial transmission blocking immunity both in vivo and in vitro.
abstract: Anti-malarial transmission-blocking vaccines (TBVs) aim to inhibit the transmission of Plasmodium from humans to mosquitoes by targeting the sexual/ookinete stages of the parasite. Successful use of such interventions will subsequently result in reduced cases of malarial infection within a human population, leading to local elimination. There are currently only five lead TBV candidates under examination. There is a consequent need to identify novel antigens to allow the formulation of new potent TBVs. Here we describe the design and evaluation of a potential TBV (BDES-PbPSOP12) targeting Plasmodium berghei PSOP12 based on the baculovirus dual expression system (BDES), enabling expression of antigens on the surface of viral particles and within infected mammalian cells. In silico studies have previously suggested that PSOP12 (Putative Secreted Ookinete Protein 12) is expressed within the sexual stages of the parasite (gametocytes, gametes and ookinetes), and is a member of the previously characterized 6-Cys family of plasmodial proteins. We demonstrate that PSOP12 is expressed within the sexual/ookinete forms of the parasite, and that sera obtained from mice immunized with BDES-PbPSOP12 can recognize the surface of the male and female gametes, and the ookinete stages of the parasite. Immunization of mice with BDES-PbPSOP12 confers modest but significant transmission-blocking activity in vivo by active immunization (53.1% reduction in oocyst intensity, 10.9% reduction in oocyst prevalence). Further assessment of transmission-blocking potency ex vivo shows a dose-dependent response, with up to a 76.4% reduction in intensity and a 47.2% reduction in prevalence observed. Our data indicates that PSOP12 in Plasmodium spp. could be a potential new TBV target candidate, and that further experimentation to examine the protein within human malaria parasites would be logical.
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: Laboratory of Vaccinology and Applied Immunology, School of Pharmacy, Kanazawa University, Ishikawa, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nishiura
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: 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: M J
authors.initials: MJ
authors.lastname: Delves
authors.affiliation: Laboratory of Vaccinology and Applied Immunology, School of Pharmacy, Kanazawa University, Ishikawa, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Iyori
authors.affiliation: Laboratory of Vaccinology and Applied Immunology, School of Pharmacy, Kanazawa University, Ishikawa, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Mizutani
authors.affiliation: Department of Life Sciences, Sir Alexander Fleming Building, Imperial College London, Imperial College Road, South Kensington, London SW7 2AZ, UK; Jenner Institute, The University of Oxford, Roosevelt Road, Oxford OX9 2PP, UK.
authors.forename: R E
authors.initials: RE
authors.lastname: Sinden
authors.affiliation: Laboratory of Vaccinology and Applied Immunology, School of Pharmacy, Kanazawa University, Ishikawa, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yoshida
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
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D016367:Baculoviridae / Q000235:genetics / Q000254:growth & development; D061505:Cell Surface Display Techniques; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D004337:Drug Carriers; D005260:Female; D008288:Malaria / Q000276:immunology* / Q000635:transmission*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D008297:Male; D008807:Mice, Inbred BALB C; D010962:Plasmodium berghei / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D004337:Drug Carriers; D017780:Malaria Vaccines
keywords: Baculovirus; Gamete; Ookinete; PSOP12; Plasmodium; Transmission-blocking