title: Comparative assessment of transmission-blocking vaccine candidates against Plasmodium falciparum.
abstract: Malaria transmission-blocking vaccines (TBVs) target the development of Plasmodium parasites within the mosquito, with the aim of preventing malaria transmission from one infected individual to another. Different vaccine platforms, mainly protein-in-adjuvant formulations delivering the leading candidate antigens, have been developed independently and have reported varied transmission-blocking activities (TBA). Here, recombinant chimpanzee adenovirus 63, ChAd63, and modified vaccinia virus Ankara, MVA, expressing AgAPN1, Pfs230-C, Pfs25, and Pfs48/45 were generated. Antibody responses primed individually against all antigens by ChAd63 immunization in BALB/c mice were boosted by the administration of MVA expressing the same antigen. These antibodies exhibited a hierarchy of inhibitory activity against the NF54 laboratory strain of P. falciparum in Anopheles stephensi mosquitoes using the standard membrane feeding assay (SMFA), with anti-Pfs230-C and anti-Pfs25 antibodies giving complete blockade. The observed rank order of inhibition was replicated against P. falciparum African field isolates in A. gambiae in direct membrane feeding assays (DMFA). TBA achieved was IgG concentration dependent. This study provides the first head-to-head comparative analysis of leading antigens using two different parasite sources in two different vector species, and can be used to guide selection of TBVs for future clinical development using the viral-vectored delivery platform.
authors.affiliation: Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
authors.forename: M C
authors.initials: MC
authors.lastname: Kapulu
authors.affiliation: Institut de Recherche en Sciences de la Santé (IRSS) et Institut de Recherche pour le Développement (IRD) - UMR MIVEGEC, Bobo-Dioulasso, Burkina Faso.
authors.forename: D F
authors.initials: DF
authors.lastname: Da
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious. Disease / National Institutes of Health, Rockville, Maryland, USA.
authors.forename: K
authors.initials: K
authors.lastname: Miura
authors.affiliation: Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Cell and Molecular Biology, Imperial College London, London, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Blagborough
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, London, UK.
authors.forename: T S
authors.initials: TS
authors.lastname: Churcher
authors.affiliation: Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
authors.forename: D
authors.initials: D
authors.lastname: Nikolaeva
authors.affiliation: Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: Williams
authors.affiliation: Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
authors.forename: A L
authors.initials: AL
authors.lastname: Goodman
authors.affiliation: Institut de Recherche en Sciences de la Santé (IRSS) et Institut de Recherche pour le Développement (IRD) - UMR MIVEGEC, Bobo-Dioulasso, Burkina Faso.
authors.forename: I
authors.initials: I
authors.lastname: Sangare
authors.affiliation: Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
authors.forename: A V
authors.initials: AV
authors.lastname: Turner
authors.affiliation: Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
authors.forename: M G
authors.initials: MG
authors.lastname: Cottingham
authors.affiliation: 1] ReiThera Srl (former Okairos Srl), Rome, Italy [2] CEINGE, Naples, Italy [3] Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Nicosia
authors.affiliation: Division of Cell and Molecular Biology, Imperial College London, London, UK.
authors.forename: U
authors.initials: U
authors.lastname: Straschil
authors.affiliation: Cell-Free Science and Technology Research Centre, Ehime University, Ehime, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tsuboi
authors.affiliation: Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
authors.forename: S C
authors.initials: SC
authors.lastname: Gilbert
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious. Disease / National Institutes of Health, Rockville, Maryland, USA.
authors.forename: Carole A
authors.initials: CA
authors.lastname: Long
authors.affiliation: 1] Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK [2] Division of Cell and Molecular Biology, Imperial College London, London, UK.
authors.forename: R E
authors.initials: RE
authors.lastname: Sinden
authors.affiliation: Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Draper
authors.affiliation: Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
authors.forename: A V S
authors.initials: AV
authors.lastname: Hill
authors.affiliation: Institut de Recherche en Sciences de la Santé (IRSS) et Institut de Recherche pour le Développement (IRD) - UMR MIVEGEC, Bobo-Dioulasso, Burkina Faso.
authors.forename: A
authors.initials: A
authors.lastname: Cohuet
authors.affiliation: Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
authors.forename: S
authors.initials: S
authors.lastname: Biswas
mesh_terms: D000818:Animals; D000852:Anopheles / Q000235:genetics / Q000276:immunology; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D009033:Culicidae / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control* / Q000635:transmission*; D051379:Mice; D010963:Plasmodium falciparum / Q000276:immunology*; D011993:Recombinant Fusion Proteins
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D011993:Recombinant Fusion Proteins