New malaria vaccine candidates based on the Plasmodium vivax Merozoite Surface Protein-1 and the TLR-5 agonist Salmonella Typhimurium FliC flagellin

New malaria vaccine candidates based on the Plasmodium vivax Merozoite Surface Protein-1 and the TLR-5 agonist Salmonella Typhimurium FliC flagellin

Autor Bargieri, Daniel Y. Autor UNIFESP Google Scholar
Rosa, Daniela S. Autor UNIFESP Google Scholar
Braga, Catarina J. M. Google Scholar
Carvalho, Bruna O. Google Scholar
Costa, Fabio Trindade Maranhão Autor UNIFESP Google Scholar
Espindola, Noeli Maria Google Scholar
Vaz, Adelaide Jose Google Scholar
Soares, Irene S. Google Scholar
Ferreira, Luis C. S. Google Scholar
Rodrigues, Mauricio M. Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Universidade Estadual de Campinas (UNICAMP)
Resumo The present study evaluated the immunogenicity of new malaria vaccine formulations based on the 19 kDa C-terminal fragment of Plasmodium vivax Merozoite Surface Protein-1 (MSP1(19)) and the Salmonella enterica serovar Typhimurium flagellin (FIiC), a Toll-like receptor 5 (TLR5) agonist. FHC was used as an adjuvant either admixed or genetically linked to the P. vivax MSP1(19) and administered to C57BL/6 mice via parenteral (s.c.) or mucosal (i.n.) routes. the recombinant fusion protein preserved MSP1(19) epitopes recognized by Sera collected from P. vivax infected humans and TLR5 agonist activity. Mice parenterally immunized with recombinant P vivax MSPI 19 in the presence of FliC, either admixed or genetically linked, elicited strong and long-lasting MSP1 (19)-specific systemic antibody responses with a prevailing IgG1 subclass response. Incorporation of another TLR agonist, CpG ODN 1826, resulted in a more balanced response, as evaluated by the IgG1/IgG2c ratio, and higher cell-mediated immune response measured by interferon-gamma secretion. Finally, we show that MSPI 19-specific antibodies recognized the native protein expressed on the surface of P. vivax parasites harvested from infected humans. the present report proposes a new class of malaria vaccine formulation based on the use of malaria antigens and the innate immunity agonist FliC. it contains intrinsic adjuvant properties and enhanced ability to induce specific humoral and cellular immune responses when administered alone or in combination with other adjuvants. (C) 2008 Elsevier B.V. All rights reserved.
Palavra-chave P vivax
Vaccine
Flagellin
FliC
TLR5
CpG ODN
TLR9
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)
The Millennium Institute for Vaccine Development and Technology
DYB
DSR
CJMB
BOC
NME
FAPESR
FTMC
AJV
LCSF
ISS
MMR
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Número do financiamento The Millennium Institute for Vaccine Development and Technology: CNPq-420067/2005-1
Data de publicação 2008-11-11
Publicado em Vaccine. Oxford: Elsevier B.V., v. 26, n. 48, p. 6132-6142, 2008.
ISSN 0264-410X (Sherpa/Romeo, fator de impacto)
Publicador Elsevier B.V.
Extensão 6132-6142
Fonte http://dx.doi.org/10.1016/j.vaccine.2008.08.070
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000261538200014
Endereço permanente http://repositorio.unifesp.br/handle/11600/31035

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