Abstract
Transmission-blocking vaccines (TBV) target the sexual-stages of the malaria parasite in the mosquito midgut and are widely considered to be an essential tool for malaria elimination. High-titer functional antibodies are required against target antigens to achieve effective transmission-blocking activity. We have fused Pfs25, the leading malaria TBV candidate antigen to IMX313, a molecular adjuvant and expressed it both in ChAd63 and MVA viral vectors and as a secreted protein-nanoparticle. Pfs25-IMX313 expressed from viral vectors or as a protein-nanoparticle is significantly more immunogenic and gives significantly better transmission-reducing activity than monomeric Pfs25. In addition, we demonstrate that the Pfs25-IMX313 protein-nanoparticle leads to a qualitatively improved antibody response in comparison to soluble Pfs25, as well as to significantly higher germinal centre (GC) responses. These results demonstrate that antigen multimerization using IMX313 is a very promising strategy to enhance antibody responses against Pfs25, and that Pfs25-IMX313 is a highly promising TBV candidate vaccine.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoviridae / genetics
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Adenoviridae / immunology
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Adjuvants, Immunologic / administration & dosage
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Adjuvants, Immunologic / chemistry
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Adjuvants, Immunologic / genetics*
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Animals
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Antibodies, Protozoan / biosynthesis*
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Antigens, Protozoan / genetics
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Antigens, Protozoan / immunology
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Culicidae / drug effects
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Culicidae / parasitology
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Gene Expression
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Genetic Vectors / chemistry
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Genetic Vectors / immunology
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Germinal Center / drug effects
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Germinal Center / immunology
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Humans
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Immunogenicity, Vaccine*
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Insect Vectors / drug effects
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Insect Vectors / parasitology
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Life Cycle Stages / drug effects
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Life Cycle Stages / immunology
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Malaria Vaccines / administration & dosage
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Malaria Vaccines / genetics
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Malaria Vaccines / immunology*
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Malaria, Falciparum / immunology
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Malaria, Falciparum / parasitology
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Malaria, Falciparum / prevention & control*
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Mice
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Mice, Inbred BALB C
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Pichia / genetics
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Pichia / metabolism
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Plasmids / chemistry
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Plasmids / immunology
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Plasmodium falciparum / drug effects*
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Plasmodium falciparum / growth & development
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Plasmodium falciparum / immunology
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Protozoan Proteins / administration & dosage
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Protozoan Proteins / genetics
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Protozoan Proteins / immunology*
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Recombinant Fusion Proteins / administration & dosage
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology
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Vaccination
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Vaccines, Synthetic
Substances
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Adjuvants, Immunologic
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Antibodies, Protozoan
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Antigens, Protozoan
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Malaria Vaccines
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Pfs25 protein, Plasmodium falciparum
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Protozoan Proteins
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Recombinant Fusion Proteins
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Vaccines, Synthetic