Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monocyte-derived dendritic cells (MoDCs) in clinical use for cancer immunotherapy are ideally generated in serum-free medium (SFM) with inclusion of a suitable maturation factor toward the end of the incubation period. Three good manfacturing practice (GMP) grade SFMs (AIM-V, X-VIVO 15, and X-VIVO 20) were compared with RPMI-1640, supplemented with 10% fetal bovine serum or 10% human serum. DCs generated for 7 days in SFM were less mature and secreted less interleukin (IL) 12p70 and IL-10 than DCs generated in 10% serum. DC yield was comparable in SFMs, and a greater proportion of cells was viable after maturation. Toll-like receptor (TLR) ligands were compared for their ability to induce cytokine secretion under serum-free conditions in the presence of interferon (IFN) gamma. With the exception of Poly I:C, TLR ligands stimulated high levels of IL-10 secretion. High levels of IL-12p70 were induced by two TLR4-mediated stimuli, lipopolysaccharide and Ribomunyl, a clinical-grade bacterial extract. When T-cell responses were compared in allogeneic mixed leukocyte reaction, DCs stimulated with Ribomunyl induced higher levels of IFNgamma than DCs stimulated with the cytokine cocktail: tumor necrosis factor-alpha, IL-1beta, IL-6, and prostaglandin E2. In the presence of IL-10 neutralizing antibodies, DC IL-12p70 production and T-cell IFNgamma were increased in vitro. Similarly, DCs stimulated with Ribomunyl, IFNgamma, and anti-IL-10 induced high levels of tetanus toxoid-specific T-cell proliferation and IFNgamma secretion. Thus, MoDCs generated in SFM efficiently stimulate T-cell IFNgamma production after maturation in the presence of a clinical-grade TLR4 agonist and IL-10 neutralization.
 ...
PMID:Generation and maturation of dendritic cells for clinical application under serum-free conditions. 1622 78

Dendritic cells (DCs) are critical antigen presentation cells whose influence on murine immune responses to polysaccharide antigens has only recently been elucidated. Little is known about human DC-polysaccharide interactions. We set out to study the interaction between human monocyte-derived DCs and pneumococcal capsular polysaccharides (PPS) in vitro. Immature DCs were generated from peripheral blood monocytes and incubated with fluorescein isothiocyanate-labeled PPS type 9N or 14 for assessment of uptake. DCs were exposed to PPS type 1, 6B, 9N, 14, 19F, or 23F in the absence or presence of Escherichia coli lipopolysaccharide (LPS) for assessment of phenotypic DC maturation and cytokine production. PPS were taken up by immature DCs and proceeded to HLA-DR+ and lysosome-associated membrane protein-1+ late endosomal compartments. Uptake was reduced in the presence of cytochalasin D and wortmannin, suggesting that both cytoskeletal rearrangements and phosphatidylinositol 3-kinase activation may be required for internalization. None of the PPS tested induced DC phenotype changes, maturation, or interleukin-12 (IL-12)/IL-10 production. However, PPS were capable of modulating the response of the DCs to a second signal such as LPS. Exposure of DCs to PPS in the presence of LPS resulted in an altered cytokine balance with significantly increased IL-10 production and reduced IL-12 production compared to LPS alone. This effect was not seen using the control antigen tetanus toxoid. DC-pneumococcus interaction may affect subsequent immune responses to pneumococci, as an altered cytokine balance may have a profound effect on DC-driven T-cell priming.
 ...
PMID:Pneumococcal polysaccharides interact with human dendritic cells. 1649 64

We evaluated the adjuvant properties and toxicity of purified Neisseria meningitidis serogroup B lipopolysaccharide (LPS) conjugated with tetanus toxoid (TT) using a new method of conjugation to obtain amine groups in the polysaccharide structure. The endotoxic activity of treated LPS was reduced 2400 times as determined by Limulus amoebocyte assay and no mortality was observed in Balb/c mice inoculated with detoxified LPS versus 100% mortality in native LPS inoculated mice. The conjugated LPS-TT elicited in mice higher anti-TT IgG2a and IgG1 than unconjugated TT. In addition, high levels of anti-LPS IgG and IgG subclasses were detected in sera. These results evidence the adjuvant activity of detoxified LPS and may suggest that the conjugation to TT changes the LPS immune response from thymus-independent to thymus-dependent.
 ...
PMID:Adjuvant properties of lipopolysaccharide from Neisseria meningitidis serogroup B detoxified and conjugated with tetanus toxoid. 1682 31

The lipopolysaccharide (LPS) of Vibrio cholerae is considered one of the most important antigens from the point of view of immunogenicity in these bacteria. We have undertaken detoxification of this LPS by basic hydrolysis and the resultant amine groups were used for their conjugation to tetanus toxoid as carrier protein using carbodiimide-mediated coupling. The resulting conjugates were inoculated in Balb/c mice for immunogenicity studies. The anti-LPS IgG and vibriocidal antibodies were measured in serum. The antigenicity of this conjugated was evaluated by ELISA, with serums of humans vaccinated with a strain genetically modified. The conjugated elicited: high titers of IgG anti-LPS, high titers of vibriocidal antibodies and there was recognition of LPS by antibodies from cholerae immunised human serum. These results show that the conjugated LPS obtained by us, could be evaluated like a potential vaccine for human use.
 ...
PMID:Preparation and evaluation of vibrio cholerae O1 EL Tor Ogawa lipopolysaccharide-tetanus toxoid conjugates. 1682 35

Environmental shedding of genetically manipulated microorganisms is an issue impeding the development of new live vaccines. We have investigated the immunogenicity of a number of novel Salmonella enterica serotype Typhimurium oral vaccine candidates that express the fragment C (TetC) component of tetanus toxin and harbor combinations of additional mutations in genes shdA, misL, and ratB that contribute to the persistence of serotype Typhimurium's colonization of the intestine. Serotype Typhimurium aroA (TetC) derivatives harboring additional mutations in either shdA or misL or combinations of these mutations exhibited a marked decrease in shedding of the vaccine strain in the feces of orally vaccinated mice. However, equivalent levels of anti-TetC and anti-Salmonella lipopolysaccharide immunoglobulin G (IgG), IgG1, IgG2a, and IgA were detected in sera of the vaccinated but not of the control mice. Cellular immune responses to TetC were detected in all vaccinated mice, regardless of the presence of the additional mutations in shdA or misL. Further, immunization with serotype Typhimurium aroA candidate vaccines harboring shdA and misL afforded complete protection against challenge with a virulent strain of serotype Typhimurium.
 ...
PMID:Candidate live, attenuated Salmonella enterica serotype Typhimurium vaccines with reduced fecal shedding are immunogenic and effective oral vaccines. 1729 64

Pertussis is an infectious disease of the respiratory tract that is caused by the gram-negative bacterium Bordetella pertussis. Although acellular pertussis (aP) vaccines are safe, they are not fully effective and thus require improvement. In contrast to whole-cell pertussis (wP) vaccines, aP vaccines do not contain lipopolysaccharide (LPS). Monophosphoryl lipid A (MPL) and Neisseria meningitidis LpxL2 LPS have been shown to display immune-stimulating activity while exerting little endotoxin activity. Therefore, we evaluated whether these LPS analogs could increase the efficacy of the aP vaccine. Mice were vaccinated with diphtheria-tetanus-aP vaccine with aluminum, MPL, or LpxL2 LPS adjuvant before intranasal challenge with B. pertussis. Compared to vaccination with the aluminum adjuvant, vaccination with either LPS analog resulted in lower colonization and a higher pertussis toxin-specific serum immunoglobulin G level, indicating increased efficacy. Vaccination with either LPS analog resulted in reduced lung eosinophilia, reduced eosinophil numbers in the bronchoalveolar lavage fluid, and the ex vivo production of interleukin-4 (IL-4) by bronchial lymph node cells and IL-5 by spleen cells, suggesting reduced type I hypersensitivity. Vaccination with either LPS analog increased serum IL-6 levels, although these levels remained well below the level induced by wP, suggesting that supplementation with LPS analogs may induce some reactogenicity but reactogenicity considerably less than that induced by the wP vaccine. In conclusion, these results indicate that supplementation with LPS analogs forms a promising strategy that can be used to improve aP vaccines.
 ...
PMID:Lipopolysaccharide analogs improve efficacy of acellular pertussis vaccine and reduce type I hypersensitivity in mice. 1749 41

Previous studies have shown that Peyer's patches (PP) are not required for intestinal immunoglobulin A (IgA) responses to orally administered soluble protein. However, the roles of PP in regulation of mucosal immune responses against bacterial antigen remain to be clarified. In the present study, we generated several gut-associated lymphoreticular tissue-null mice by treatment with anti-interleukin-7 receptor antibody, the fusion protein of lymphotoxin beta receptor and IgG Fc, and/or tumor necrosis factor receptor p55 and IgG Fc. These mice were then immunized with recombinant Salmonella expressing the C fragment of the tetanus toxin (rSalmonella-Tox C). Orally immunized PP-null mice as well as isolated lymphoid follicle (ILF)-null, PP/ILF-null, and PP/ILF/mesenteric lymph node-null mice induced identical levels of tetanus toxoid (TT)-specific systemic IgG responses to those of control mice. However, PP-null mice, but not ILF-null mice, failed to induce TT-specific intestinal IgA antibodies. Analysis of TT-specific CD4+ T-cell responses showed a reduction of gamma interferon (IFN-gamma) synthesis in the intestinal lamina propriae of PP-null mice given oral rSalmonella-Tox C. In contrast, TT-specific IFN-gamma responses in the spleen and delayed-type hypersensitivity responses were intact in those immunized mice. Interestingly, Salmonella lipopolysaccharide (LPS)-specific fecal IgA responses were not elicited in PP-null mice, while serum IgG anti-LPS antibodies were identical to those of control mice. These results suggest that while none of the gut-associated lymphoreticular tissues are required for the induction of systemic immune responses, PP are an essential lymphoid tissue for induction and regulation of intestinal IgA immunity against orally administered rSalmonella.
 ...
PMID:Peyer's patches are required for intestinal immunoglobulin A responses to Salmonella spp. 1808 15

Live Salmonella vaccines are limited in use by the inherent toxicity of the lipopolysaccharide. The waaN gene encodes a myristyl transferase required for the secondary acylation of lipid A in lipopolysaccharide. A waaN mutant exhibits reduced induction of the inflammatory cytokines associated with lipopolysaccharide toxicity. Here the characteristics of a Salmonella enterica serovar Typhimurium aroA waaN mutant (SK100) in vitro and in vivo compared with its parent aroA strain (SL3261) were described. Phenotypic analysis of purified lipopolysaccharide obtained from SK100 confirmed that the physical and biological activities of the lipopolysaccharide had been altered. Nevertheless both strains had similar patterns of colonization and persistence in mice and significantly the aroA waaN mutant was equally as effective as the parent at protecting against challenge with wild-type S. Typhimurium. Furthermore, a SK100 strain was constructed expressing both tetanus toxin fragment C and the circumsporozoite protein of a malaria parasite. In marked contrast to its isogenic parent, the new attenuated strain induces significantly enhanced immune responses against the circumsporozoite protein. The waaN mutation enhances the ability of this strain to elicit immune responses towards guest antigens. This study provides important insights into the development of safe and effective multivalent Salmonella vaccines.
 ...
PMID:Genetic detoxification of an aroA Salmonella enterica serovar Typhimurium vaccine strain does not compromise protection against virulent Salmonella and enhances the immune responses towards a protective malarial antigen. 1817 43

There is a general trend that parasitism risk declines as latitude increases. Host populations breeding at high latitudes should therefore invest less in costly immune defenses than populations breeding in temperate or tropical zones, although it is unknown if such an effect is mediated by environmental (photoperiodic) or genetic factors or both. Acquired immune function (humoral, cell-mediated) and behavioral sickness responses to lipopolysaccharide (LPS; mimics bacterial infection) were assessed in two subspecies of white-crowned sparrow (Zonotrichia leucophrys) that breed at different latitudes in western North America. Zonotrichia l. gambelii (GWCS) is a high-latitude breeder (47-68 degrees N) while Z. l. pugetensis (PWCS) breeds at temperate latitudes (40-49 degrees N). Captive males of each subspecies were acclimated to (1) a short day (non-breeding) photoperiod (8L:16D), (2) the breeding photoperiod of PWCS (16L:8D), or (3) the breeding photoperiod of GWCS (20L:4D). Photoperiod was manipulated because shorter day lengths may enhance immune function. In support of a genetic effect, humoral responses to diphtheria-tetanus vaccination were significantly higher in PWCS compared to GWCS, regardless of photoperiod. There were no differences in cell-mediated responses to phytohemagglutinin (PHA) between subspecies or among photoperiods. For sickness responses to LPS, a significant interaction between photoperiod and subspecies was found, with long day GWCS producing stronger sickness responses (losing more weight, eating less) than short day GWCS and PWCS on all day lengths. However, these effects were influenced by photoperiodic changes in body condition. In conclusion, we find evidence for genetic control of immune responses across latitude, but no support for environmental (photoperiodic) regulation.
 ...
PMID:Latitudinal variation of immune defense and sickness behavior in the white-crowned sparrow (Zonotrichia leucophrys). 1825 57

An approach to vaccine design is the use of molecules that mimic the immunogenic element of interest. In this context, the interaction of MDWNMHAA, a peptide mimic of the Shigella flexneri Y O polysaccharide (PS), with an anti-carbohydrate monoclonal antibody, as studied previously by X-ray crystallography, suggested the presence of functional rather than structural mimicry and a bound peptide conformation that was not represented significantly in the free-ligand ensemble. The antibody response elicited by an MDWNMHAA-carrier protein (tetanus toxoid [TT]) conjugate has now been investigated in BALB/c mice. The mice were immunized following a homologous prime/boost strategy using MDWNMHAA-TT as the immunogen. The mice showed anti-peptide antibody (immunoglobulin G [IgG]) titers that increased after being boosted. High anti-lipopolysaccharide (LPS) (IgG) titers were observed after the last boost. A faster immune response, with cross-reactive titers, was observed with a peptide conjugate with 30% more copies of the peptide. The binding of anti-peptide polyclonal antibodies to LPS could be inhibited by LPS, PS, MDWNMHAA, and MDWNMHAA-bovine serum albumin, as assessed by inhibition enzyme-linked immunosorbent assay. Conversely, mice immunized with PS-TT showed IgG anti-peptide titers. These data demonstrate the cross-reactivity of the antibody response and support the hypothesis that functional, as opposed to structural, mimicry of the S. flexneri Y O PS by MDWNMHAA or the underrepresentation of the bound ligand conformation in the free-ligand ensemble does not compromise immunological cross-reactivity. Prime/boost strategies were performed with a heterologous boost of PS-TT or MDWNMHAA-TT. They led to high anti-LPS titers after only three injections, suggesting alternatives to improve the immunogenicity of the carbohydrate-mimetic peptide and confirming the antigenic mimicry.
 ...
PMID:Immunological evidence for functional rather than structural mimicry by a Shigella flexneri Y polysaccharide-mimetic peptide. 1846 26


<< Previous 1 2 3 4 5 6 7 8 9 10