The stage-specific in vitro efficacy of a malaria antigen cocktail provides valuable insights into the development of effective multi-stage vaccines.
Multicomponent vaccines targeting different stages of Plasmodium falciparum represent a promising, holistic concept towards better malaria vaccines. Additionally, an effective vaccine candidate should demonstrate cross-strain specificity because many antigens are polymorphic, which can reduce vaccine efficacy. A cocktail of recombinant fusion proteins (VAMAX-Mix) featuring three diversity-covering variants of the blood-stage antigen PfAMA1, each combined with the conserved sexual-stage antigen Pfs25 and one of the pre-erythrocytic-stage antigens PfCSP_TSR or PfCelTOS, or the additional blood-stage antigen PfMSP1_19, was produced in Pichia pastoris and used to immunize rabbits. The immune sera and purified IgG were used to perform various assays determining antigen specific titers and in vitro efficacy against different parasite stages and strains. In functional in vitro assays we observed robust inhibition of blood-stage (up to 90%), and sexual-stage parasites (up to 100%) and biased inhibition of pre-erythrocytic parasites (0-40%). Cross-strain blood-stage efficacy was observed in erythrocyte invasion assays using four different P. falciparum strains. The quantification of antigen-specific IgGs allowed the determination of specific IC50 values. The significant difference in antigen-specific IC50 requirements, the direct correlation between antigen-specific IgG and the relative quantitative representation of antigens within the cocktail, provide valuable implementations for future multi-stage, multi-component vaccine designs.
Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany. holger.spiegel@ime.fraunhofer.de.
Holger
H
Spiegel
Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany.
Alexander
A
Boes
Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany.
Robin
R
Kastilan
Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany.
Stephanie
S
Kapelski
Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany.
Güven
G
Edgue
Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany.
Veronique
V
Beiss
Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany.
Ivana
I
Chubodova
Zentrum für Infektionsforschung, Wuerzburg, Germany.
Matthias
M
Scheuermayer
RWTH Aachen University, Institute of Molecular Biotechnology, Aachen, Germany.
Gabriele
G
Pradel
Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany.
Stefan
S
Schillberg
Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany.
Andreas
A
Reimann
Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany.|RWTH Aachen University, Institute of Molecular Biotechnology, Aachen, Germany.
Rainer
R
Fischer
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology / Q000627:therapeutic use; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D006801:Humans; D008288:Malaria / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D017780:Malaria Vaccines / Q000276:immunology* / Q000627:therapeutic use; D010843:Pichia / Q000235:genetics; D010963:Plasmodium falciparum / Q000276:immunology* / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000276:immunology* / Q000627:therapeutic use
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; C071284:Pfs25 protein, Plasmodium falciparum; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins
Parasite growth inhibition; Pichia pastoris; Plasmodium falciparum; Recombinant fusion proteins; Transmission blocking assay