Jennings H J
Division of Biological Sciences, National Research Council of Canada, Ottawa, Ontario.
Adv Exp Med Biol. 1988;228:495-550. doi: 10.1007/978-1-4613-1663-3_18.
Capsular polysaccharides have assumed an important role as vaccines against disease caused by bacteria in humans. The concept of using pure definable polysaccharides devoid of their accompanying complex bacterial mass is technically elegant and is obviously capable of extension into other areas of immunoprophylaxis. However, problems have been identified which will need to be solved in order that the concept may be more widely adopted. Focusing on the meningococcal polysaccharides, possible solutions to two of these important problems, namely, the poor immunogenicity of the A and C polysaccharides in infants, and the poor immunogenicity of the B polysaccharide in all humans, are proposed. These solutions involve the use of a new generation of artificial synthetic antigens for modulating the immune response. For instance, conjugation of the A and C polysaccharides to tetanus toxoid converted them to T-cell dependent antigens in mice, thus making these conjugates potential infant vaccine candidates. Although a similar conjugation of the B polysaccharide failed to substantially enhance its immunogenicity in mice, this could be achieved by further chemical manipulation of the basic structure of the B polysaccharide. N-propionylation of the B polysaccharide, followed by its conjugation to tetanus toxoid, yielded an antigen, which when injected in mice, induced in them high titers of cross-reactive B polysaccharide-specific IgG antibodies. The chemical modification of polysaccharides requires an understanding of the interrelation between their structures and immunospecificities, and the structural elucidation of polysaccharides and the resultant monitoring of their structural modifications, can be conveniently accomplished using a wide range of NMR spectroscopic techniques. The capsular polysaccharides of many of the bacteria which cause meningitis in humans contain sialic acid and have extensive structural homology with human tissue. As a result of this homology the immunospecificities of these polysaccharides are complex, being based on unconventional conformational determinants.
荚膜多糖作为预防人类细菌性疾病的疫苗已发挥重要作用。使用不含伴随复杂细菌成分的纯可定义多糖的概念在技术上很精妙，显然能够扩展到免疫预防的其他领域。然而，已发现一些问题，若要使该概念得到更广泛应用，这些问题需要解决。以脑膜炎球菌多糖为例，针对其中两个重要问题提出了可能的解决方案，即A和C多糖在婴儿中免疫原性较差，以及B多糖在所有人中免疫原性较差。这些解决方案涉及使用新一代人工合成抗原调节免疫反应。例如，将A和C多糖与破伤风类毒素偶联，使其在小鼠中转变为T细胞依赖性抗原，从而使这些偶联物成为潜在的婴儿疫苗候选物。虽然B多糖的类似偶联未能在小鼠中显著增强其免疫原性，但可通过对B多糖基本结构的进一步化学操作来实现。对B多糖进行N-丙酰化，然后与破伤风类毒素偶联，产生一种抗原，将其注射到小鼠体内时，可诱导小鼠产生高滴度的交叉反应性B多糖特异性IgG抗体。多糖的化学修饰需要了解其结构与免疫特异性之间的相互关系，利用多种核磁共振光谱技术可方便地完成多糖的结构解析及其结构修饰的监测。许多导致人类脑膜炎的细菌的荚膜多糖含有唾液酸，且与人体组织具有广泛的结构同源性。由于这种同源性，这些多糖的免疫特异性很复杂，基于非常规的构象决定簇。
