Weintraub Andrej
Karolinska Institute, Department of Laboratory Medicine, Division of Clinical Bacteriology, Huddinge University Hospital, S-141 86 Stockholm, Sweden.
Carbohydr Res. 2003 Nov 14;338(23):2539-47. doi: 10.1016/j.carres.2003.07.008.
Carbohydrates in the form of capsular polysaccharides and/or lipopolysaccharides are the major components on the surface of bacteria. These molecules are important virulence factors in many bacteria isolated from infected persons. Immunity against these components confers protection against the disease. However, developing vaccines based on polysaccharides is difficult and several problems have to be solved. First of all, most of the bacterial polysaccharides are T-lymphocyte independent antigens. Anti-polysaccharide immune response is characterised by lack of T-lymphocyte memory, isotype restriction and delayed ontogeny. Children below 2 years of age and elderly respond poorly to polysaccharide antigens. Secondly, the wide structural heterogeneity among the polysaccharides within and between species is also a problem. Thirdly, some bacterial polysaccharides are poor immunogens in humans due to their structural similarities with glycolipids and glycoproteins present in man. The T-lymphocyte independent nature of a polysaccharide may be overcome by conjugating the native or depolymerised polysaccharide to a protein carrier. Such neoglycoconjugates have been proven to be efficient in inducing T-lymphocyte dependent immunity and to protect both infants as well as elderly from disease. Another approach to circumvent the T-lymphocyte independent property of polysaccharides is to select peptides mimicking the immunodominant structures. Several examples of such peptides have been described.
以荚膜多糖和/或脂多糖形式存在的碳水化合物是细菌表面的主要成分。这些分子是从感染者体内分离出的许多细菌中的重要毒力因子。针对这些成分的免疫可提供对疾病的保护。然而,基于多糖开发疫苗很困难,必须解决几个问题。首先,大多数细菌多糖是T淋巴细胞非依赖性抗原。抗多糖免疫反应的特点是缺乏T淋巴细胞记忆、同种型限制和发育延迟。2岁以下儿童和老年人对多糖抗原的反应较差。其次,不同物种内部和之间多糖的广泛结构异质性也是一个问题。第三,一些细菌多糖由于其与人存在的糖脂和糖蛋白结构相似,在人体内是弱免疫原。多糖的T淋巴细胞非依赖性特性可以通过将天然或解聚的多糖与蛋白质载体偶联来克服。这种新糖缀合物已被证明在诱导T淋巴细胞依赖性免疫以及保护婴儿和老年人免受疾病侵害方面是有效的。另一种规避多糖T淋巴细胞非依赖性特性的方法是选择模拟免疫显性结构的肽。已经描述了此类肽的几个例子。