126 results about "Lipid A" patented technology

A demineralized bone putty composition comprises: (1) demineralized bone matrix (DBM); and (2) a lipid fraction selected from the group consisting of lecithin and a mixture of lecithin and triglycerides containing unsaturated fatty acids. The putty composition is moldable, biocompatible, slowly resorbable, and soluble in tissue fluids, and non-extrudable. The composition delivers a biologically active product to animals and humans that will enhance bone formation at sites where bone is lost, deficient, or present in suboptimal amounts. The composition can further comprise calcium, an antioxidant such as Vitamin E or Vitamin C, or a hydrophilic polymer such as methylcellulose or hydroxypropyl methylcellulose.

Specific fractions of Vitreoscilla filiformis comprising its Lipid A are useful for stimulating the synthesis of anti-microbial peptides of the skin.

The core structure of pentaerythritol has been used as a replacement for one or both sugars in lipid A, leading to the generation of a series of lipid A analogs. These lipid A analogs may further differ from lipid A with respect to, e.g., the number, nature and location of negatively charged groups, and the number, nature and location of the lipid chains. The lipid A analogs may be lipid A agonists useful as immunostimulatory agents, or lipid A antagonists useful in the treatment of septic shock. In a like manner, a residue of pentaerythritylamine may be used as a replacement for an amino sugar residue in a carbohydrate ligand having a biological activity of interest, generating a series of ligand analogs. These are useful, e.g., as haptens, inhibitors of bacterial-host cell adhesion, etc.

Provided herein are mutant strains of Neisseria meningitidis which produce Kdo-free lipid A as well as the Kdo-free lipid A molecules and immunogenic compositions containing such Kdo-free lipid A molecules from a Neisseria strain containing a genetically stable mutation which inactivates a gene selected from the group consisting of genes encoding arabinose-5-phosphate isomerase, CMP-Kdo synthetase and CMP-Kdo transferase. N. meningitidis NMB206 is a specifically exemplified strain which harbors a stable insertion mutation in the gene (ApsF) encoding A5P isomerase; strain NMB-249 is a specifically exemplified strain with a stable insertion mutation in the gene (kdtA) encoding CMP-Kdo synthetase, and strain NMB259 is specifically exemplified strain with a stable insertion mutation in the gene (kdsB) encoding CMP-Kdo transferase. Also provided by the present invention are methods for the production of Lipid A flee of 3-keto-3-deoxyoctanoic acid using these genetically stable N. meningitidis mutants. Also describes is pYT250, a plasmid functional in neisseriae and in enterics such as Escherichia coli.

The invention provides functionalized monosaccharides and disaccharides suitable for use in synthesizing a lipid A derivative, as well as methods for synthesizing and using a synthetic lipid A derivative.

The invention discloses preparation and application of a low-toxicity Kdo2-monophosphoryl lipid A containing five fatty acid chains, belonging to the field of bioengineering. By modifying Escherichia coli, a special-structure low-toxicity five-chain Kdo2-monophosphoryl lipid A is synthesized, and the Kdo2-lipid A molecule is not connected with the core polysaccharide long chain, and only composed of two 2-one-3-desoxyoctoic acids, five fatty acid chains and a C4' site single phosphoric acid. The Kdo2-lipid A is amphiphilic, is convenient for separation, extraction and purification, can be detected and directly identified, maintains the biological immunocompetence of the lipid A part, has obvious toxicity attenuation effect as compared with wild type W3110 LPS, and is a vaccine adjuvant with great development potential. Meanwhile, the method for extracting and purifying the Kdo2-lipid A is simple in steps and easy to operate.

A method for immunization using genetic material is disclosed. Compositions for genetic immunization comprising cationic lipids and polynucleotides are also disclosed. Methods for using genetic immunization to produce polyclonal and monoclonal antibodies are also disclosed. A method for epitope mapping is also disclosed.

The present invention relates to Neisserial Lipo-Oligo-Saccharides (LOS) that comprise a tri-saccharide outer core that shows increased binding to the DC-SIGN receptor on dendritic cells, as a result of which the Neisserial LOS's of the invention have increased immunostimulatory activity. The tri-saccharide outer core of the Neiserial LOS's combined with a Lipid A moiety with reduced toxicity is useful as an adjuvant in vaccine preparations.

Fraction A of Quil A can be used together with at least one other adjuvant for the preparation of an adjuvant composition, where the included adjuvant components act synergistically to enhance level of immune response and have synergistic immunomodulating activity on the co-administered antigens or immunogens.Other adjuvants can comprise saponins, naturally occurring, synthetic or semisynthetic saponin molecules; e.g. saponins and saponin fractions from Quil A, cell wall skeleton, blockpolymers, TDM, lipopeptides, LPS and LPS-derivatives, Lipid A from different bacterial species and derivatives thereof, e.g., monophosphoryl lipid A. CpG variants, CT and LT or fractions thereof.

The invention provides a series of novel Lipid A analogs that are structually simple, synthetically accessible, and capable of blocking the cellular receptor within the signal transduction pathway. The novel Lipid A analogs can include a monosaccharide core with hydrophobic side chains and amino acid ionic motif. The invention further provides methods of using the compounds and compositions thereof in various therapeutic methods.

A method for cryopreservation of animal cells with high level of intracellular lipid content, comprises the steps of conducting a delipation procedure using one or more lipolytic agent(s) and / or lipogenesis inhibitors during culture of the animal cells to stimulate the hydrolysis of intracellular lipids to reduce the lipid content, and vitrifying the treated animal cells using a modified vitrification solution and a modified warming solution.

A process for producing hydrocarbons from microbial lipids is provided by contacting a feed comprising microbial lipids with a hydrogenation catalyst and hydrogen at a temperature in the range of from 250 to 380° C. and a total pressure in the range of from 20 to 160 bar (absolute), to obtain an effluent comprising paraffinic hydrocarbons and water; optionally separating a liquid stream rich in paraffinic hydrocarbons from the effluent; contacting the paraffinic hydrocarbons in the liquid stream rich in paraffinic hydrocarbons or the effluent comprising paraffinic hydrocarbons by contacting hydrogen and the liquid stream with hydroisomerisation catalyst at a temperature in the range of from 280 to 450° C. and a total pressure in the range of from 20 to 160 bar (absolute); and separating at least one product fraction from the product stream obtained, wherein the hydrogenation catalyst and / or the hydroisomerisation catalyst comprises a sulfided hydrogenation catalyst.

Recombinant fragments of Factor C are disclosed. These proteins and peptides show great potency in recognizing, binding to, neutralizing and removing endotoxin. These molecules can thus be used for anti-microbial, anti-endotoxin, and anti-sepsis therapy. SSCrFCES is a 38 kDa protein representing the LPS-binding domain of Factor C. The ability of SSCrFCES to bind lipid A was analyzed using an ELISA-based assay as well as surface plasmon resonance. Surface plasmon resonance similarly carried out for SSCrFC-sushi-1,2,3-GFP, SSCrFC-sushi-1GFP, and SSCrFC-sushi-3GFP confirmed their superior affinity for endotoxin. The 50% endotoxin-neutralizing concentration of SSCrFCES against 200 EU of endotoxin is 0.069 μM, suggesting that SSCrFCES is an effective inhibitor of LAL coagulation cascade. Although partially attenuated by human serum, as low as 1 μM of SSCrFCES inhibits the LPS-induced secretion of hTNF-α and hIL-8 by THP-1 and human pheripheral blood mononuclear cells with a potency more superior than polymyxin B. SSCrFCES is non-cytotoxic, with a clearance rate of 4.7 ml / minute. The LD90 of SSCrFCES for LPS lethality in mice is achieved at 2 μM. These results demonstrate the endotoxin-neutralizing capability of SSCrFCES in vitro and in vivo, as well as its potential for use in the treatment of endotoxin-induced septic shock. Also embodied in this application is the use of the sushi peptides and their mutant derivatives as potent antimicrobials.

Engineered bacteria are provided that produce modified lipid A and a polypeptide or polysaccharide antigens. In some aspects, immunogenic compositions are provided comprising a modified a lipid A and a polypeptide or polysaccharide antigen.