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

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dc.contributor.authorCamacho, Ariane Guglielmi Ariza [UNIFESP]
dc.contributor.authorTeixeira, Lais Helena [UNIFESP]
dc.contributor.authorBargieri, Daniel Youssef [UNIFESP]
dc.contributor.authorBoscardin, Silvia Beatriz
dc.contributor.authorSoares, Irene da Silva
dc.contributor.authorNussenzweig, Ruth Sonntag
dc.contributor.authorNussenzweig, Victor
dc.contributor.authorRodrigues, Mauricio Martins [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionNYU
dc.date.accessioned2018-06-18T11:04:02Z
dc.date.available2018-06-18T11:04:02Z
dc.date.issued2011-08-01
dc.description.abstractRecently, 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.en
dc.description.affiliationUniv Fed Sao Paulo, Escola Paulista Med, Ctr Terapia Celular & Mol, BR-04044010 Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, BR-04044010 Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Dept Parasitol, Inst Ciencia Biomed, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, Sao Paulo, Brazil
dc.description.affiliationNYU, Sch Med, Dept Pathol, Michael Heidelberger Div, New York, NY USA
dc.description.affiliationNYU, Sch Med, Dept Med & Mol Parasitol, New York, NY USA
dc.description.affiliationUnifespUniv Fed Sao Paulo, Escola Paulista Med, Ctr Terapia Celular & Mol, BR-04044010 Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, BR-04044010 Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipManlio Cantarini fellowship
dc.description.sponsorshipIDFAPESP: 2009/15132-4
dc.format.extent167-171
dc.identifierhttp://dx.doi.org/10.1590/S0074-02762011000900021
dc.identifier.citationMemorias Do Instituto Oswaldo Cruz. Rio De Janeiro, Rj: Fundaco Oswaldo Cruz, v. 106, n. S1, p. 167-171, 2011.
dc.identifier.doi10.1590/S0074-02762011000900021
dc.identifier.fileS0074-02762011000900021.pdf
dc.identifier.issn0074-0276
dc.identifier.scieloS0074-02762011000900021
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/44891
dc.identifier.wosWOS:000294440600021
dc.language.isoeng
dc.publisherFundaco Oswaldo Cruz
dc.relation.ispartofMemorias Do Instituto Oswaldo Cruz
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectTLR5en
dc.subjectflagellinen
dc.subjectCS proteinen
dc.subjectP. vivaxen
dc.titleTLR5-dependent immunogenicity of a recombinant fusion protein containing an immunodominant epitope of malarial circumsporozoite protein and the FliC flagellin of Salmonella Typhimuriumen
dc.typeinfo:eu-repo/semantics/article
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