TLR5-dependent immunogenicity of a recombinant fusion protein containing an immunodominant epitope of malarial circumsporozoite protein and the FliC flagellin of Salmonella typhimurium



Título del documento: TLR5-dependent immunogenicity of a recombinant fusion protein containing an immunodominant epitope of malarial circumsporozoite protein and the FliC flagellin of Salmonella typhimurium
Revista: Memorias do Instituto Oswaldo Cruz
Base de datos: PERIÓDICA
Número de sistema: 000349636
ISSN: 0074-0276
Autores: 1
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5
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Instituciones: 1Universidade Federal de Sao Paulo, Escola Paulista de Medicina, Sao Paulo. Brasil
2Universidade de Sao Paulo, Instituto de Ciencias Biomedicas, Sao Paulo. Brasil
3Universidade de Sao Paulo, Faculdade de Ciencias Farmaceuticas, Sao Paulo. Brasil
4University School of Medicine, Michael Heidelberger Division, Nueva York. Estados Unidos de América
5University School of Medicine, Department of Medical and Molecular Parasitology, Nueva York. Estados Unidos de América
Año:
Volumen: 106
País: Brasil
Idioma: Inglés
Tipo de documento: Artículo
Enfoque: Experimental, aplicado
Resumen en inglés Recently, we described the improved immunogenicity of new malaria vaccine candidates based on the expression of fusion proteins containing immunodominant epitopes of merozoites and Salmonella enterica serovar Typhimurium flagellin (FliC) protein as an innate immune agonist. Here, we tested whether a similar strategy, based on an immunodominant B-cell epitope from malaria sporozoites, could also generate immunogenic fusion polypeptides. A recombinant His6-tagged FliC protein containing the C-terminal repeat regions of the VK210 variant of Plasmodium vivax circumsporozoite (CS) protein was constructed. This recombinant protein was successfully expressed in Escherichia coli as soluble protein and was purified by affinity to Ni-agarose beads followed by ion exchange chromatography. A monoclonal antibody specific for the CS protein of P. vivax sporozoites (VK210) was able to recognise the purified protein. C57BL/6 mice subcutaneously immunised with the recombinant fusion protein in the absence of any conventional adjuvant developed protein-specific systemic antibody responses. However, in mice genetically deficient in expression of TLR5, this immune response was extremely low. These results extend our previous observations concerning the immunogenicity of these recombinant fusion proteins and provide evidence that the main mechanism responsible for this immune activation involves interactions with TLR5, which has not previously been demonstrated for any recombinant FliC fusion protein
Disciplinas: Medicina
Palabras clave: Parasitología,
Inmunología,
Paludismo,
Flagelina,
Proteínas de fusión,
Inmunogenicidad,
Plasmodium vivax
Keyword: Medicine,
Parasitology,
Immunology,
Malaria,
Flagellin,
Fusion proteins,
Immunogenicity,
Plasmodium vivax
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