Agradecimentos: This work was supported by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), the Millennium Institute for Vaccine Development and Technology (CNPq - 420067/2005-1), the National Institute for Vaccine Development and Technology (CNPq - INCTV), and Rede de...

Agradecimentos: This work was supported by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), the Millennium Institute for Vaccine Development and Technology (CNPq - 420067/2005-1), the National Institute for Vaccine Development and Technology (CNPq - INCTV), and Rede de Malária (CNPq). DYB, JAL, SCPL and CJMB were supported by fellowships from FAPESP. MES-A, LCSF, ISS, FTMC and MMR were supported by fellowships from CNPq

In a recent study, we demonstrated the immunogenic properties of a new malaria vaccine polypeptide based on a 19 kDa C-terminal fragment of the merozoite surface protein-1 (MSP119) from Plasmodium vivax and an innate immunity agonist, the Salmonella enterica serovar Typhimurium flagellin (FliC)....

In a recent study, we demonstrated the immunogenic properties of a new malaria vaccine polypeptide based on a 19 kDa C-terminal fragment of the merozoite surface protein-1 (MSP119) from Plasmodium vivax and an innate immunity agonist, the Salmonella enterica serovar Typhimurium flagellin (FliC). Herein, we tested whether the same strategy, based on the MSP119 component of the deadly malaria parasite Plasmodium falciparum, could also generate a fusion polypeptide with enhanced immunogenicity. The His6FliC-MSP119 fusion protein was expressed from a recombinant Escherichia coli and showed preserved in vitro TLR5-binding activity. In contrast to animals injected with His6MSP119, mice subcutaneously immunised with the recombinant His6FliC-MSP119 developed strong MSP119-specific systemic antibody responses with a prevailing IgG1 subclass. Incorporation of other adjuvants, such as CpG ODN 1826, complete and incomplete Freund's adjuvants or Quil-A, improved the IgG responses after the second, but not the third, immunising dose. It also resulted in a more balanced IgG subclass response, as evaluated by the IgG1/IgG2c ratio, and higher cell-mediated immune response, as determined by the detection of antigen-specific interferon-γ secretion by immune spleen cells. MSP119-specific antibodies recognised not only the recombinant protein, but also the native protein expressed on the surface of P. falciparum parasites. Finally, sera from rabbits immunised with the fusion protein alone inhibited the in vitro growth of three different P. falciparum strains. In summary, these results extend our previous observations and further demonstrate that fusion of the innate immunity agonist FliC to Plasmodium antigens is a promising alternative to improve their immunogenicity

FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP

CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ

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