Immunogenic properties of a recombinant fusion protein containing theC-terminal 19 kDa of Plasmodium falciparum merozoite surface protein-1 and the innate immunity agonist FliC flagellin of Salmonella Typhimurium
Vaccine
; 28(16): 2818-2826, 2010.
Article
em En
| SES-SP, SESSP-IBPROD, SES-SP, SESSP-IBACERVO
| ID: biblio-1068346
Biblioteca responsável:
BR78.1
Localização: BR78.1
ABSTRACT
In a recent study, we demonstrated the immunogenic properties of a new malaria vaccine polypeptidebased on a 19 kDa C-terminal fragment of the merozoite surface protein-1 (MSP119) from Plasmodiumvivax 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 malariaparasite Plasmodium falciparum, could also generate a fusion polypeptide with enhanced immunogenicity.The His6FliC-MSP119 fusion protein was expressed from a recombinant Escherichia coli and showedpreserved in vitro TLR5-binding activity. In contrast to animals injected with His6MSP119, mice subcutaneouslyimmunised with the recombinant His6FliC-MSP119 developed strong MSP119-specific systemicantibody responses with a prevailing IgG1 subclass. Incorporation of other adjuvants, such as CpG ODN1826, complete and incomplete Freunds 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, asevaluated by the IgG1/IgG2c ratio, and higher cell-mediated immune response, as determined by thedetection of antigen-specific interferon- secretion by immune spleen cells. MSP119-specific antibodiesrecognised 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 invitro growth of three different P. falciparum strains. In summary, these results extend our previous observationsand further demonstrate that fusion of the innate immunity agonist FliC to Plasmodium antigensis a promising alternative to improve their immunogenicity
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Coleções:
06-national
/
BR
Base de dados:
SES-SP
/
SESSP-IBACERVO
/
SESSP-IBPROD
Assunto principal:
Salmonella typhimurium
/
Flagelina
Limite:
Humans
Idioma:
En
Revista:
Vaccine
Ano de publicação:
2010
Tipo de documento:
Article