title: Analysis of a Multi-component Multi-stage Malaria Vaccine Candidate--Tackling the Cocktail Challenge.
abstract: Combining key antigens from the different stages of the P. falciparum life cycle in the context of a multi-stage-specific cocktail offers a promising approach towards the development of a malaria vaccine ideally capable of preventing initial infection, the clinical manifestation as well as the transmission of the disease. To investigate the potential of such an approach we combined proteins and domains (11 in total) from the pre-erythrocytic, blood and sexual stages of P. falciparum into a cocktail of four different components recombinantly produced in plants. After immunization of rabbits we determined the domain-specific antibody titers as well as component-specific antibody concentrations and correlated them with stage specific in vitro efficacy. Using purified rabbit immune IgG we observed strong inhibition in functional in vitro assays addressing the pre-erythrocytic (up to 80%), blood (up to 90%) and sexual parasite stages (100%). Based on the component-specific antibody concentrations we calculated the IC50 values for the pre-erythrocytic stage (17-25 μg/ml), the blood stage (40-60 μg/ml) and the sexual stage (1.75 μg/ml). While the results underline the feasibility of a multi-stage vaccine cocktail, the analysis of component-specific efficacy indicates significant differences in IC50 requirements for stage-specific antibody concentrations providing valuable insights into this complex scenario and will thereby improve future approaches towards malaria vaccine cocktail development regarding the selection of suitable antigens and the ratios of components, to fine tune overall and stage-specific efficacy.
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Aachen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Boes
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Aachen, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Spiegel
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Aachen, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Voepel
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Aachen, Germany.
authors.forename: Gueven
authors.initials: G
authors.lastname: Edgue
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Aachen, Germany.
authors.forename: Veronique
authors.initials: V
authors.lastname: Beiss
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Aachen, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kapelski
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Aachen, Germany; RWTH Aachen University, Institute of Molecular Biotechnology, Aachen, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Fendel
authors.affiliation: Zentrum für Infektionsforschung, Wuerzburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Scheuermayer
authors.affiliation: RWTH Aachen University, Institute of Molecular Biotechnology, Aachen, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pradel
authors.affiliation: TropIQ Health Sciences, Nijmegen, The Netherlands.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Bolscher
authors.affiliation: Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Marije C
authors.initials: MC
authors.lastname: Behet
authors.affiliation: TropIQ Health Sciences, Nijmegen, The Netherlands.
authors.forename: Koen J
authors.initials: KJ
authors.lastname: Dechering
authors.affiliation: Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Cornelus C
authors.initials: CC
authors.lastname: Hermsen
authors.affiliation: TropIQ Health Sciences, Nijmegen, The Netherlands; Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Aachen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schillberg
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Aachen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Reimann
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Aachen, Germany; RWTH Aachen University, Institute of Molecular Biotechnology, Aachen, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Fischer
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D007114:Immunization; D017780:Malaria Vaccines / Q000627:therapeutic use*; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control*; D010963:Plasmodium falciparum / Q000276:immunology*; D011817:Rabbits
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines