Immunogenic properties of a recombinant fusion protein containing the C-terminal 19 kDa of Plasmodium falciparum merozoite surface protein-1 and the innate immunity agonist FliC flagellin of Salmonella Typhimurium

Immunogenic properties of a recombinant fusion protein containing the C-terminal 19 kDa of Plasmodium falciparum merozoite surface protein-1 and the innate immunity agonist FliC flagellin of Salmonella Typhimurium

Autor Bargieri, Daniel Y. Autor UNIFESP Google Scholar
Leite, Juliana A. Google Scholar
Lopes, Stefanie C. P. Google Scholar
Sbrogio-Almeida, Maria Elisabete Google Scholar
Braga, Catarina J. M. Google Scholar
Ferreira, Luis C. S. Google Scholar
Soares, Irene S. Google Scholar
Costa, Fabio Trindade Maranhão Autor UNIFESP Google Scholar
Rodrigues, Mauricio M. Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Universidade Estadual de Campinas (UNICAMP)
Lab Ctr Biotecnol
Universidade de São Paulo (USP)
Fac Ciencias Farmaceut
Resumo 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 (MSP1(19)) 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 MSP1(19) component of the deadly malaria parasite Plasmodium falciparum, could also generate a fusion polypeptide with enhanced immunogenicity. the His(6)FliC-MSP1(19) fusion protein was expressed from a recombinant Escherichia coli and showed preserved in vitro TLR5-binding activity. in contrast to animals injected with His(6)MSP1(19), mice subcutaneously immunised with the recombinant His6FliC-MSP1(19) developed strong MSP1(19)-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-gamma secretion by immune spleen cells. MSP19-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. (c) 2010 Elsevier B.V. All rights reserved.
Palavra-chave P. falciparum
Vaccine
Flagellin
TLR5
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Millennium Institute for Vaccine Development and Technology
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Número do financiamento Millennium Institute for Vaccine Development and Technology: CNPq 420067/2005-1
Data de publicação 2010-04-01
Publicado em Vaccine. Oxford: Elsevier B.V., v. 28, n. 16, p. 2818-2826, 2010.
ISSN 0264-410X (Sherpa/Romeo, fator de impacto)
Publicador Elsevier B.V.
Extensão 2818-2826
Fonte http://dx.doi.org/10.1016/j.vaccine.2010.02.004
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000276972100005
Endereço permanente http://repositorio.unifesp.br/handle/11600/32435

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