Navegando por Palavras-chave "CpG ODN"

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    Cross-priming of long lived protective CD8(+) T cells against Trypanosoma cruzi infection: Importance of a TLR9 agonist and CD4(+) T cells
    (Elsevier B.V., 2007-08-10) Alencar, Bruna C. G. de; Araujo, Adriano F. S.; Penido, Marcus L. O.; Gazzinelli, Ricardo T.; Rodrigues, Mauricio M.; Universidade Federal de São Paulo (UNIFESP); Fiocruz MS; Universidade Federal de Minas Gerais (UFMG)
    We recently described that vaccination of mice with a gluthatione S transferase fusion protein representing amino acids 261-500 of the Amastigote Surface Protein-2 efficiently cross-primed protective CD8(+) T cells against a lethal challenge with the human protozoan parasite Trypanosoma cruzi. in this study, we initially established that this protective immunity was long lived. Subsequently, we studied the importance of TLR9 agonist CpG ODN 1826, TLR4 and CD4(+) T cells for the generation of these protective CD8(+) T cells. We found that: (i) the TLR9 agonist CpG ODN 1826 improved the efficiency of protective immunity; (ii) TLR4 is not relevant for priming of specific CD8(+) T cells; (iii) CD4(+) T cells are critical for priming of memory/protective CD8(+) T cells. (c) 2007 Elsevier B.V. All rights reserved.
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    New malaria vaccine candidates based on the Plasmodium vivax Merozoite Surface Protein-1 and the TLR-5 agonist Salmonella Typhimurium FliC flagellin
    (Elsevier B.V., 2008-11-11) Bargieri, Daniel Y. [UNIFESP]; Rosa, Daniela S. [UNIFESP]; Braga, Catarina J. M.; Carvalho, Bruna O.; Costa, Fabio Trindade Maranhão [UNIFESP]; Espindola, Noeli Maria; Vaz, Adelaide Jose; Soares, Irene S.; Ferreira, Luis C. S.; Rodrigues, Mauricio M. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); Universidade Estadual de Campinas (UNICAMP)
    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.
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    Role of interferon-gamma during CpG oligodeoxynucleotide-adjuvanted immunization with recombinant proteins
    (Elsevier B.V., 2007-08-10) Rosa, Daniela Santoro; Bastos, Karina R.; Bargieri, Daniel Youssef; Tzelepis, Fanny; Nomizo, Auro; Russo, Momtchilo; Soares, Irene S.; Rodrigues, Mauricio M.; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
    Synthetic oligonucleotides (ODNs) containing immunostimulatory CpG motifs (CpG) are a new class of adjuvants suitable for the development of recombinant vaccines. Here we describe that endogenous interferon (IFN) was critical for the adjuvant activity of CpG ODN as genetically deficient mice developed significantly lower IgG antibody titers following immunization with recombinant proteins. in contrast, the absence of endogenous IL-12/IL-23 or IL-4 had little impact on the magnitude of the antibody response but instead caused a dramatic change in the pattern of IgG isotypes. the dependence on IFN-gamma was specific for CpG ODN and it was not observed with other adjuvants tested. IFN-gamma was produced by NK, dendritic cells, CD4(+) and CD8(+) T cells stimulated in vitro with CpG ODN. Adoptive transfer experiments confirmed that CD4(+) or CD8(+) T cells were in fact relevant sources of IFN-gamma in vivo. Following CpG ODN injection, splenic dendritic cells from IFN-gamma deficient mice did not up-regulate CD86 or CD40 expression, suggesting a role for these molecules. the importance of CD28 (CD86 ligand) was confirmed using CD28 deficient mice which presented severely impaired immune responses following CpG ODN-assisted immunization. (c) 2007 Elsevier B.V. All rights reserved.