Abstract:
:Listeriolysin O (LLO) has been proposed as a potential carrier or adjuvant molecule in the vaccination field. However, the cytotoxic and pro-apoptotic effects of LLO are the major limitations for this purpose. Here, we have performed a preclinical safety evaluation and characterized a new potential adjuvant application for a non-cytolytic LLO mutant (dtLLO) to enhance and modulate the immune response against the envelope (E) protein from dengue virus. In addition, we have studied the adjuvant effects of dtLLO on human immune cells and the role of membrane cholesterol for the binding and proinflammatory property of the toxoid. Our in-vivo results in the murine model confirmed that dtLLO is a safer molecule than wild-type LLO (wtLLO), with a significantly increased survival rate for mice challenged with dtLLO compared with mice challenged with wtLLO (P < 0·001). Histopathological analysis showed non-toxic effects in key target organs such as brain, heart, liver, spleen, kidney and lung after challenge with dtLLO. In vitro, dtLLO retained the capacity of binding to plasma membrane cholesterol on the surface of murine and human immune cells. Immunization of 6-8-week-old female BALB/c mice with a combination of dtLLO mixed with E protein elicited a robust specific humoral response with isotype diversification of immunoglobulin (Ig)G antibodies (IgG1 and IgG2a). Finally, we demonstrated that cholesterol and lipid raft integrity are required to induce a proinflammatory response by human cells. Taken together, these findings support a potential use of the dtLLO mutant as a safe and effective adjuvant molecule in vaccination.
journal_name
Clin Exp Immunoljournal_title
Clinical and experimental immunologyauthors
Hernández-Flores KG,Calderón-Garcidueñas AL,Mellado-Sánchez G,Ruiz-Ramos R,Sánchez-Vargas LA,Thomas-Dupont P,Izaguirre-Hernández IY,Téllez-Sosa J,Martínez-Barnetche J,Wood L,Paterson Y,Cedillo-Barrón L,López-Franco O,Vivanco-Cidoi
10.1111/cei.12906subject
Has Abstractpub_date
2017-04-01 00:00:00pages
109-126issue
1eissn
0009-9104issn
1365-2249journal_volume
188pub_type
杂志文章abstract::We have recently demonstrated that peripheral blood monocytes from patients with multiple sclerosis (MS) have a defect in stimulating autologous and allogeneic T lymphocytes. This defect was found to correlate with disease activity. In this report we demonstrate that prothymosin alpha (ProT alpha), a rat thymus fracti...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1987-11-01 00:00:00
abstract::Membranous nephropathy (MN), the leading cause of nephrotic syndrome in adults, is characterized by the deposition of subepithelial immune deposits that consist mainly of immunoglobulin (Ig)G and complement. Most of the cases are primary or idiopathic (iMN), while only approximately 25% of the cases are secondary to s...
journal_title:Clinical and experimental immunology
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章,评审
doi:10.1111/cei.13280
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2249.2006.02996.x
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abstract::Serum inhibition factors (SIF) that suppress phytohaemagglutinin-induced blast transformation of normal lymphocytes, and lymphocyte E-rosette inhibitory factors (RIF) that inhibit the T cell-specific property of E-rosette formation were determined in sixty-five patients before and after cardiac surgery. SIF was found ...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1979-11-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1976-10-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1989-09-01 00:00:00
abstract::A method has been developed for separating eosinophils from other types of leucocyte in normal individuals. Erythrocytes are sedimented with dextran, and mononuclear cells are removed on an isotonic density gradient of ficoll and sodium diatrizoate. The eosinophils and neutrophils are then washed and sedimented onto p...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1977-05-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1978-03-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2249.2007.03517.x
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/cei.13574
更新日期:2021-01-12 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2249.1995.tb03840.x
更新日期:1995-12-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2249.1994.tb06029.x
更新日期:1994-01-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1987-07-01 00:00:00
abstract::Natural killer (NK) cell adoptive transfer is a promising approach for cancer immunotherapy; however, its development has been hindered by the lack of efficient methods to produce large numbers of functional NK cells. In this study, we engineered the leukaemia cell line K562 to express CD137 ligand (CD137L) and membra...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/cei.12034
更新日期:2013-04-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1981-07-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1981-11-01 00:00:00
abstract::Proliferative responses by human peripheral blood mononuclear cells and rat spleen cells were measured to Pneumocystis carinii in a blastogenic assay using organisms obtained from rat lungs and propagated in tissue culture as the antigen. Responses occurred only in subjects with known prior exposure to P. carinii and ...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1988-10-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2249.2005.02934.x
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1977-04-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1981-07-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1989-03-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/cei.12325
更新日期:2014-07-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章,评审
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更新日期:2011-01-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章,评审
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更新日期:2002-05-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/cei.12899
更新日期:2017-03-01 00:00:00
abstract::The influence of human seminal plasma (SP) and whole semen (S) on the expression of natural cytotoxicity by human peripheral blood mononuclear cells (PBMNC) was examined. Marked suppression of natural cytotoxicity against K562 targets was observed when effectors were pre-treated for 1 h with SP or S diluted up to 1:40...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1986-03-01 00:00:00
abstract::Sjögren's syndrome (SS) is characterized by a focal periductal salivary gland infiltrate consisting mainly of T and B lymphocytes. Most of the T cells bear the memory CD4+ Th1-like phenotype and express high levels of class II, though CD8+ cells are also present. We have studied 17 labial salivary gland and 15 periphe...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1046/j.1365-2249.1996.d01-623.x
更新日期:1996-02-01 00:00:00
abstract::Reduced microbial exposure in early life may contribute to the increase of atopic diseases in 'westernized' societies but the underlying mechanisms remain elusive. The objective of this study was to examine how exposure to bacterial lipopolysaccharide (LPS) during early antigen encounter might influence the maturation...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2249.2005.02706.x
更新日期:2005-02-01 00:00:00