title: Baculovirus-vectored multistage Plasmodium vivax vaccine induces both protective and transmission-blocking immunities against transgenic rodent malaria parasites.
abstract: A multistage malaria vaccine targeting the pre-erythrocytic and sexual stages of Plasmodium could effectively protect individuals against infection from mosquito bites and provide transmission-blocking (TB) activity against the sexual stages of the parasite, respectively. This strategy could help prevent malaria infections in individuals and, on a larger scale, prevent malaria transmission in communities of endemicity. Here, we describe the development of a multistage Plasmodium vivax vaccine which simultaneously expresses P. vivax circumsporozoite protein (PvCSP) and P25 (Pvs25) protein of this species as a fusion protein, thereby acting as a pre-erythrocytic vaccine and a TB vaccine, respectively. A new-concept vaccine platform based on the baculovirus dual-expression system (BDES) was evaluated. The BDES-Pvs25-PvCSP vaccine displayed correct folding of the Pvs25-PvCSP fusion protein on the viral envelope and was highly expressed upon transduction of mammalian cells in vitro. This vaccine induced high levels of antibodies to Pvs25 and PvCSP and elicited protective (43%) and TB (82%) efficacies against transgenic P. berghei parasites expressing the corresponding P. vivax antigens in mice. Our data indicate that our BDES, which functions as both a subunit and DNA vaccine, can offer a promising multistage vaccine capable of delivering a potent antimalarial pre-erythrocytic and TB response via a single immunization regimen.
authors.affiliation: Laboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Mizutani
authors.affiliation: Laboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Iyori
authors.affiliation: Division of Cell and Molecular Biology, Department of Life Sciences, Imperial College London, London, United Kingdom.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Blagborough
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Fukumoto
authors.affiliation: Laboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Funatsu
authors.affiliation: Division of Cell and Molecular Biology, Department of Life Sciences, Imperial College London, London, United Kingdom.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Sinden
authors.affiliation: Laboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa, Japan shigeto@p.kanazawa-u.ac.jp.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D016367:Baculoviridae / Q000235:genetics; D018562:Disease Transmission, Infectious / Q000517:prevention & control; D004337:Drug Carriers; D005260:Female; D005822:Genetic Vectors; D008288:Malaria / Q000517:prevention & control* / Q000635:transmission; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010962:Plasmodium berghei / Q000235:genetics / Q000276:immunology; D010966:Plasmodium vivax / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D004337:Drug Carriers; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan; C067548:ookinete antigen P25, Plasmodium
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