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SYNTHETIC VACCINE AGAINST SHIGELLOSIS

SYNTHETIC VACCINE AGAINST SHIGELLOSIS
志贺氏菌合成疫苗
批准号:
5203361
负责人:
V POZSGAY
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:

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中文摘要
翻译
由志贺氏痢疾杆菌1型引起的志贺氏菌病仍然是主要疾病
英文摘要
Shigellosis caused by Shigella dysenteriae type 1 continues to be a major enteric disease worldwide. Because of the multiple-antibiotic resistance of many strains of Shigellae, the treatment of shigellosis is difficult. Although the need for vaccines to control this disease has been documented by the WHO, there is no licenced vaccine against shigellosis. Following the discovery by Robbins and coworkers that serum antibodies against the O-specific polysaccharide (OSP) of S. dysenteriae type 1 confer protective immunity in humans we hypothesized that extended fragments of the OSP may also be suitable for the induction of protective antibodies when coupled to immunogenic proteins, provided that the conformational ensemble of such saccharides approaches that of the conformational determinant of the native polysaccharide. The use of synthetic saccharides of defined structure instead of polysaccharides of complex architecture is likely to offer advantages including enhanced uniformity of conjugates and elimination of the analytical difficulties associated with the established, polysaccharide-protein vaccines. Based on this hypothesis we are developing synthetic oligo- and poly-saccharide-based immunogens of well-defined characteristics. We designed a strategy to prepare fragments of the OSP of S. dysenteriae type 1. The OSP consists of a tetrasaccharide repeating unit that is composed of D-galactose, N-acetyl-D-glucosamine, and L-rhamnose. Starting from monosaccharide building blocks that carry orthogonal protecting and activating groups, a tetrasaccharide donor/acceptor molecule was assembled. Iterative combination of this building block afforded di-, tri- and tetramers of the repeating unit corresponding to octa-, dodeca- and hexadeca-saccharides. Nuclear magnetic resonance spectroscopy indicated that the dodeca- and the hexadeca-saccharides exhibit a high degree of conformational similarity to the native O-SP which we believe is a prerequisite for protective antibody induction. In vitro experiments showed that the synthetic saccharides inhibit the binding of the OSP to homologous monoclonal antibodies.
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SYNTHETIC VACCINE AGAINST SHIGELLOSIS
ISOLATION AND PURIFICATION OF SUBUNIT B OF SHIGA TOXIN
ISOLATION AND PURIFICATION OF SUBUNIT B OF SHIGA TOXIN
ANALYSIS AND SYNTHESIS OF CARBOHYDRATE ANTIGENS OF MYCOBACTERIUM TUBERCULOSIS
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海外基金
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