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Glycoconjugate vaccines: some observations on carrier and production methods.
Biotechnology and Genetic Engineering Reviews ( IF 6.5 ) Pub Date : 2020-02-12 , DOI: 10.1080/02648725.2019.1703614
Thomas E MacCalman 1 , Mary K Phillips-Jones 1 , Stephen E Harding 1, 2
Affiliation  

Glycoconjugate vaccines use protein carriers to improve the immune response to polysaccharide antigens. The protein component allows the vaccine to interact with T cells, providing a stronger and longer-lasting immune response than a polysaccharide interacting with B cells alone. Whilst in theory the mere presence of a protein component in a vaccine should be sufficient to improve vaccine efficacy, the extent of improvement varies. In the present review, a comparison of the performances of vaccines developed with and without a protein carrier are presented. The usefulness of analytical tools for macromolecular integrity assays, in particular nuclear magnetic resonance, circular dichroism, analytical ultracentrifugation and SEC coupled to multi-angle light scattering (MALS) is indicated. Although we focus mainly on bacterial capsular polysaccharide-protein vaccines, some consideration is also given to research on experimental cancer vaccines using zwitterionic polysaccharides which, unusually for polysaccharides, are able to invoke T-cell responses and have been used in the development of potential all-polysaccharide-based cancer vaccines.A general trend of improved immunogenicity for glycoconjugate vaccines is described. Since the immunogenicity of a vaccine will also depend on carrier protein type and the way in which it has been linked to polysaccharide, the effects of different carrier proteins and production methods are also reviewed. We suggest that, in general, there is no single best carrier for use in glycoconjugate vaccines. This indicates that the choice of carrier protein is optimally made on a case-by-case basis, based on what generates the best immune response and can be produced safely in each individual case.Abbreviations: AUC: analytical ultracentrifugation; BSA: bovine serum albumin; CD: circular dichroism spectroscopy; CPS: capsular polysaccharide; CRM197: Cross Reactive Material 197; DT: diphtheria toxoid; Hib: Haemophilius influenzae type b; MALS: multi-angle light scattering; Men: Neisseria menigitidis; MHC-II: major histocompatibility complex class II; NMR: nuclear magnetic resonance spectroscopy; OMP: outer membrane protein; PRP: polyribosyl ribitol phosphate; PSA: Polysaccharide A1; Sa: Salmonella; St.: Streptococcus; SEC: size exclusion chromatography; Sta: Staphylococcus; TT: tetanus toxoid; ZPS: zwitterionic polysaccharide(s).

中文翻译:

糖缀合物疫苗:关于载体和生产方法的一些观察。

糖缀合物疫苗使用蛋白质载体来改善对多糖抗原的免疫反应。蛋白质成分使疫苗能够与T细胞相互作用,从而比单独与B细胞相互作用的多糖提供更强和更持久的免疫反应。从理论上讲,疫苗中仅存在蛋白质成分就足以提高疫苗效力,但改善程度却有所不同。在本综述中,提供了在有和没有蛋白质载体的情况下开发的疫苗性能的比较。指出了用于大分子完整性测定的分析工具的有用性,特别是核磁共振,圆二色性,分析超速离心和与多角度光散射(MALS)耦合的SEC。尽管我们主要关注细菌荚膜多糖蛋白疫苗,但也考虑了使用两性离子多糖对实验性癌症疫苗进行研究的方法,两性离子多糖通常对多糖具有激活T细胞反应的能力,并已被用于开发潜在的所有疾病。 -基于多糖的癌症疫苗。描述了糖缀合物疫苗的免疫原性提高的一般趋势。由于疫苗的免疫原性还取决于载体蛋白的类型以及其与多糖的连接方式,因此还对不同载体蛋白的作用和生产方法进行了综述。我们建议,一般而言,在糖缀合物疫苗中没有单一的最佳载体。这表明载体蛋白的选择是根据具体情况进行最佳选择的,缩写:AUC:分析超速离心;根据产生最佳免疫反应的物质而定,可以在每种情况下安全产生。BSA:牛血清白蛋白;CD:圆二色光谱;CPS:荚膜多糖;CRM197:交叉反应材料197;DT:白喉类毒素;Hib:b型流感嗜血杆菌;MALS:多角度光散射;男性:脑膜炎奈瑟菌;MHC-II:II类主要组织相容性复合物;NMR:核磁共振波谱;OMP:外膜蛋白;PRP:聚核糖核糖醇磷酸酯;PSA:多糖A1;萨:沙门氏菌;St .:链球菌;SEC:体积排阻色谱法;Sta:葡萄球菌;TT:破伤风类毒素;ZPS:两性离子多糖。分析超速离心 BSA:牛血清白蛋白;CD:圆二色光谱;CPS:荚膜多糖;CRM197:交叉反应材料197;DT:白喉类毒素;Hib:b型流感嗜血杆菌;MALS:多角度光散射;男性:脑膜炎奈瑟菌;MHC-II:II类主要组织相容性复合物;NMR:核磁共振波谱;OMP:外膜蛋白;PRP:聚核糖核糖醇磷酸酯;PSA:多糖A1;萨:沙门氏菌;St .:链球菌;SEC:尺寸排阻色谱法;Sta:葡萄球菌;TT:破伤风类毒素;ZPS:两性离子多糖。分析超速离心 BSA:牛血清白蛋白;CD:圆二色光谱;CPS:荚膜多糖;CRM197:交叉反应材料197;DT:白喉类毒素;Hib:b型流感嗜血杆菌;MALS:多角度光散射;男性:脑膜炎奈瑟菌;MHC-II:II类主要组织相容性复合物;NMR:核磁共振波谱;OMP:外膜蛋白;PRP:聚核糖核糖醇磷酸酯;PSA:多糖A1;萨:沙门氏菌;St .:链球菌;SEC:体积排阻色谱法;Sta:葡萄球菌;TT:破伤风类毒素;ZPS:两性离子多糖。多角度光散射;男性:脑膜炎奈瑟菌;MHC-II:II类主要组织相容性复合物;NMR:核磁共振波谱;OMP:外膜蛋白;PRP:聚核糖核糖醇磷酸酯;PSA:多糖A1;萨:沙门氏菌;St .:链球菌;SEC:体积排阻色谱法;Sta:葡萄球菌;TT:破伤风类毒素;ZPS:两性离子多糖。多角度光散射;男性:脑膜炎奈瑟菌;MHC-II:II类主要组织相容性复合物;NMR:核磁共振波谱;OMP:外膜蛋白;PRP:聚核糖核糖醇磷酸酯;PSA:多糖A1;萨:沙门氏菌;St .:链球菌;SEC:体积排阻色谱法;Sta:葡萄球菌;TT:破伤风类毒素;ZPS:两性离子多糖。
更新日期:2020-04-20
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