Enhancing immunogenicity and transmission-blocking activity of malaria vaccines by fusing Pfs25 to IMX313 multimerization technology
| Autor: | Yuanyuan, Li, Darren B, Leneghan, Kazutoyo, Miura, Daria, Nikolaeva, Iona J, Brian, Matthew D J, Dicks, Alex J, Fyfe, Sarah E, Zakutansky, Simone, de Cassan, Carole A, Long, Simon J, Draper, Adrian V S, Hill, Fergal, Hill, Sumi, Biswas |
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| Rok vydání: | 2015 |
| Předmět: |
Recombinant Fusion Proteins
Genetic Vectors Plasmodium falciparum Protozoan Proteins Antibodies Protozoan Gene Expression Antigens Protozoan Pichia Article Adenoviridae Mice Immunogenicity Vaccine Adjuvants Immunologic parasitic diseases Malaria Vaccines Animals Humans Malaria Falciparum Life Cycle Stages Mice Inbred BALB C Vaccines Synthetic Vaccination Germinal Center Insect Vectors Culicidae Plasmids |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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