Goldblatt D
Immunobiology Unit, Institute of Child Health and Great Ormond Street Hospital for Children, London.
J Med Microbiol. 1998 Jul;47(7):563-7. doi: 10.1099/00222615-47-7-563.
Study of the epidemiology of childhood infection reveals that the brunt of disease for a number of invasive bacterial infections is borne by children under the age of 4 years. Haemophilus influenzae type b (Hib), Neisseria meningitidis and Streptococcus pneumoniae, the three most important causes of childhood meningitis, illustrate this phenomenon, which is caused by the inability of infants and young children to mount antibodies to the carbohydrates that form a capsule surrounding these organisms. Carbohydrates are traditionally viewed as T-independent antigens with a number of unique and important immunological properties that are not encountered when inducing an immune response to proteins. These properties include no overt requirement for the presence of T cells to induce an immune response, dominance of IgM, failure to induce memory following immunisation, an absence of affinity maturation following immunisation, and poor immunogenicity in infants, the elderly and the immunocompromised. These properties of carbohydrates have precluded the use of pure carbohydrate vaccines in those patients most at risk. Conjugate vaccine technology, where a carbohydrate antigen is coupled chemically to a protein carrier, has overcome the limitations of carbohydrates as vaccine antigens by rendering the carbohydrate moiety of such vaccines immunogenic, even in the very young. The dramatic success of the Hib conjugate vaccines, the first conjugates licensed clinically for human use, in reducing the incidence of invasive Hib disease has demonstrated the potential value of such conjugate vaccines. Similar technology is, therefore, being applied to a number of other vaccines in development, including N. meningitidis (groups A and C) and S. pneumoniae vaccines. The large number of pneumococcal carbohydrate serotypes that require inclusion in a vaccine makes this conjugate formulation far more complicated than that for Hib, and it is likely that the dramatic success of the Hib conjugate vaccines will be more difficult to repeat for the pneumococcus.
儿童感染流行病学研究表明，许多侵袭性细菌感染的疾病负担主要由4岁以下儿童承担。b型流感嗜血杆菌（Hib）、脑膜炎奈瑟菌和肺炎链球菌是儿童脑膜炎的三个最重要病因，它们说明了这一现象，这是由于婴幼儿无法针对构成这些生物体周围荚膜的碳水化合物产生抗体所致。传统上，碳水化合物被视为非T细胞依赖性抗原，具有许多独特且重要的免疫学特性，这些特性在诱导针对蛋白质的免疫反应时不会出现。这些特性包括诱导免疫反应时对T细胞的存在没有明显要求、IgM占主导、免疫接种后不诱导记忆、免疫接种后缺乏亲和力成熟，以及在婴儿、老年人和免疫功能低下者中免疫原性较差。碳水化合物的这些特性使得在那些风险最高的患者中无法使用纯碳水化合物疫苗。结合疫苗技术是将碳水化合物抗原与蛋白质载体化学偶联，通过使此类疫苗的碳水化合物部分具有免疫原性，克服了碳水化合物作为疫苗抗原的局限性，即使在非常年幼的儿童中也是如此。Hib结合疫苗是首个获得临床许可用于人类的结合疫苗，它在降低侵袭性Hib疾病发病率方面取得了巨大成功，证明了此类结合疫苗的潜在价值。因此，类似的技术正在应用于许多其他正在研发的疫苗，包括A群和C群脑膜炎奈瑟菌疫苗以及肺炎链球菌疫苗。疫苗中需要包含大量的肺炎球菌碳水化合物血清型，这使得这种结合疫苗的配方比Hib疫苗要复杂得多，而且肺炎球菌结合疫苗可能很难重现Hib结合疫苗那样的巨大成功。
