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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Date
2011-08-01Author
Camacho, Ariane Guglielmi Ariza [UNIFESP]
Teixeira, Lais Helena [UNIFESP]
Bargieri, Daniel Youssef [UNIFESP]
Boscardin, Silvia Beatriz
Soares, Irene da Silva
Nussenzweig, Ruth Sonntag
Nussenzweig, Victor
Rodrigues, Mauricio Martins [UNIFESP]
Type
ArtigoISSN
0074-0276Is part of
Memorias Do Instituto Oswaldo CruzDOI
10.1590/S0074-02762011000900021Metadata
Show full item recordAbstract
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.
Citation
Memorias Do Instituto Oswaldo Cruz. Rio De Janeiro, Rj: Fundaco Oswaldo Cruz, v. 106, n. S1, p. 167-171, 2011.Keywords
TLR5flagellin
CS protein
P. vivax
Sponsorship
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Manlio Cantarini fellowship
Collections
- EPM - Artigos [17707]