肺炎链球菌糖类疫苗综述

Review of Streptococcus Pneumoniae Carbohydrate-Based Vaccines

肺炎链球菌是一类可诱发侵袭性疾病、严重危害人类健康的机会致病菌。随着各类细菌性疾病造成的医疗负担不断加剧以及细菌对抗生素耐药性的增强,有效防治细菌感染再次受到社会重视。疫苗接种作为一种重要的预防措施,可以有效保护易感人群免于肺炎链球菌的侵袭。荚膜多糖是肺炎链球菌的主要致病物质之一,具有较好的免疫原性,为研发糖类疫苗提供了可能性和重要依据。文章综述了肺炎链球菌的生物学特性与感染机制以及针对肺炎链球菌的糖类疫苗。目前市售的肺炎链球菌疫苗以传统糖类疫苗和结合疫苗为主,随着糖科学快速发展,合成寡糖并结合载体蛋白制备半合成糖缀合物的技术不断成熟,有助于制备诱导特异性抗体反应更快且效果更好的新型半合成结合疫苗。因此半合成结合疫苗有望逐步应用于肺炎链球菌性疾病的临床预防当中,弥补多糖疫苗和结合疫苗临床应用的不足。文章介绍了肺炎链球菌多糖疫苗、结合疫苗和半合成疫苗的免疫特点、发展现况,系统分析了多糖疫苗、结合疫苗在肺炎链球菌性疾病预防上的应用和存在的问题,并重点阐述了现阶段研发半合成结合疫苗所需糖缀合物的免疫原性与抗原性检测,为相关研究提供参考。

Streptococcus pneumoniae is a kind of opportunistic pathogen which could be induced invasive diseases and seriously harm human health.With the increasing medical burden caused by bacterial disease and the enhancement of the bacteria′s resistance to antibiotics,the prevention of bacterial infections has gradually received social attention.As an important preventive approach,vaccination can effectively protect susceptible people from infection of Streptococcus pneumoniae.As one of the main pathogenic substances of Streptococcus pneumoniae,capsular polysaccharide has excellent immunogenicity,providing the possibility and foundation for the development of carbohydrate vaccines.This article reviews the biological characteristics and infection mechanism of Streptococcus pneumoniae and the carbohydrate-based vaccines.Currently commercially available Streptococcus pneumoniae vaccines are based on traditional polysaccharide vaccines and glycan-conjugate vaccines.With the rapid development of carbohydrate science,the technology of synthesizing oligosaccharides and combining carrier proteins to prepare semisynthetic glycoconjugates has greatly developed,which helps to prepare new semisynthetic conjugate vaccines that induce specific antibody efficiently and with better effects.Therefore,semisynthetic conjugate vaccines have great potential in the application of the prevention of Streptococcus pneumoniae-induced diseases,comparing with the shortcoming of currently used polysaccharide vaccines and conjugate vaccines.This article introduced polysaccharide vaccines,conjugate vaccines and semisynthetic conjugate vaccines of Streptococcus pneumoniae,systematically analyzes the application and existing problems of polysaccharide vaccines and conjugate vaccines in the prevention of Streptococcus pneumoniae-induced diseases.It also emphasized the studies of immunogenicity and antigenicity of oligosaccharide hapten at present stage,providing a reference for the development of semisynthetic conjugate vaccine.