A detoxified recombinant E. coli heat-labile enterotoxin mutant, LTS61K, is employed as a carrier protein to conjugate polysaccharide. The LTS61K contains a mutated mature sub-unit A (LTA) that includes lysine at amino acid position 61 and a wild-type mature sub-unit B (LTB). Various types of bacterial capsular polysaccharide antigens were chemically conjugated with the LTS61K protein by a reductive amination reaction. The conjugated polysaccharide-LTS61K products were physically, chemically and biochemically identified as soluble form. Rabbits were immunized intramuscularly to determine the immunogenicity of conjugated vaccines by ELISA to detect anti-polysaccharide antigen IgG titers and serum bactericidal assay thereby determining the functional activity of the antibodies. Study results show that conjugated polysaccharide-LTS61K vaccines induce higher polysaccharide-specific IgG titers and greater bactericidal activity in sera than that of polysaccharide alone or polysaccharide mixed with LTS61K. The presence of anti-LTS61K serum IgG antibody alleviates travel diarrhea caused by E. coli (ETEC enterotoxigenic E. coli).

Hsu; Yu-Shen

Kou; I-Ling

Hung; Kuo-Chan

Lu; Yuan-Hsin

Yuan; Ta-Tung

DEVELOPMENT CENTER FOR BIOTECHNOLOGY

Polysaccharide conjugation with detoxified E. coli heat labile enterotoxin (LT) used as vaccine

Disclosed are compositions, methods, and kits for treating conditions including; ameliorating side effects associated with compounds such as lipase inhibitors; gastrointestinal distress; fecal urgency; obesity; hyperlipidemia; diarrhea; reducing levels of toxic substances; reducing blood cholesterol levels; inducing satiety; effecting weight loss; effecting weight control; and treating, delaying onset and/or preventing Type II diabetes. One embodiment includes compositions for administration to an animal for stiffening lipophilic substances in the gastrointestinal tract. Such stiffening agents have a complete melting point of about 33.degree. C. or greater. Kits comprising the composition are also included. Methods of stiffening lipophilic substances present in the gastrointestinal tract of an animal are also provided. The methods comprise administering a composition comprising a safe and effective amount of a stiffening agent to an animal. The methods also comprise administering a composition comprising a safe and effective amount of a stiffening agent and a safe and effective amount of a lipase inhibitor to an animal.

Jandacek; Ronald James

Francis; William Randall

Kelm; Gary Robert

Hird; Bryn

The Procter &amp; Gamble Company

Compositions, methods, and kits useful for the alleviation of gastrointestinal effects

Imino sugars, such as deoxynojirimycin (DNJ), are glucose analogues that selectively inhibit cellular .alpha.-glucosidase I and II (enzymes that process N-linked glycans in glycoprotein) and exhibit broad spectrum antiviral activities against many enveloped viruses. Previously we have reported a novel DNJ derivative, OSL-95II, with antiviral activity and reduced cytotoxicity. In order to develop imino sugars with more potent antiviral activity as well as improved toxicity profile, OSL-95II was modified by diversifying the nitrogen linked alkylated side chain. The antiviral activities were initially tested in bovine viral diarrhea virus (BVDV) infected MDBK cells, yielding several imino sugar derivatives with novel structure and superior antiviral activity and toxicity profile. Furthermore, these new compounds were shown to be active against Dengue virus (DV) and West Nile virus (WNV) infection in BHK cells where potent anti-DV activity having submicromolar EC50 values and SI of greater than 900. These compounds represent a new generation of iminio sugars and their analogues, having application in the clinical treatment of infection of DV and other members of flaviviridae.

Block; Timothy M.

Chang; Jinhong

Xu; Xiaodong

Baruch S. Blumberg Institute

Drexel University

Imino sugar derivatives demonstrate potent antiviral activity and reduced toxicity

greater

diarrhea

greater/diarrhea

Polysaccharide conjugation with detoxified E. coli heat labile enterotoxin (LT) used as vaccine

Compositions, methods, and kits useful for the alleviation of gastrointestinal effects

Imino sugar derivatives demonstrate potent antiviral activity and reduced toxicity

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