Preparation and evaluation of immunogenic conjugates of Salmonella enterica serovar Typhi O-specific polysaccharides with diphtheria toxoid.
Preparation and evaluation of immunogenic conjugates of Salmonella enterica serovar Typhi O-specific polysaccharides with diphtheria toxoid.
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DOI：
10.4161/hv.18350
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发表时间：
2012-02-01
影响因子：
4.8
通讯作者：
Carbis, Rodney
中科院分区：
文献类型：
--
作者：
Ali, Aamir;An, So Jung;Carbis, Rodney
伤寒是由肠沙门氏菌血清型伤寒（S. Typhi）引起的，是一个主要的健康问题，特别是在发展中国家。现有的疫苗在效力方面有一定的局限性，不能引起免疫反应，特别是在2岁以下的个体中。结合疫苗由细菌特异性多糖与载体蛋白化学结合组成，通过诱导具有增强免疫原性特征的t细胞依赖性免疫反应克服了这些问题。本研究以己二酸二肼（ADH）为连接体，将伤寒沙门氏菌o特异性多糖（OSP）与白喉类毒素（DT）结合。这些偶联物（OSP-AH-DT）的免疫原性以小鼠为模型进行了评估，结果显示IgG ELISA滴度水平显著高于单独的脂多糖（P = 0.0241和0.0245）。比较不同的免疫接种方案，发现方案b（间隔4周注射3次）诱导的免疫应答高于方案a（间隔2周注射3次）。我们发现白喉类毒素可以成功地作为载体蛋白与沙门氏菌OSP结合，并在促进充分的免疫反应中发挥重要作用。
Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a major health problem particularly in developing countries. The available vaccines have certain limitations regarding their efficacy, and inability to induce an immune response especially in individuals under 2 years of age. Conjugate vaccines which consist of a bacteria-specific polysaccharide chemically bound to a carrier protein overcome these problems by inducing a T-cell dependent immune response characterized by enhanced immunogenicity in all ages. In this study, O-specific polysaccharides (OSP) of S. Typhi were conjugated to diphtheria toxoid (DT) using adipic acid dihydrazide (ADH) as a linker. These conjugates (OSP-AH-DT) were then evaluated for their immunogenicity using mice as a model and showed significantly higher levels of IgG ELISA titers (P = 0.0241 and 0.0245) than lipopolysaccharides alone. Different immunization schedules were compared and it was found that schedule-B (three injections with 4-weeks interval) induced higher immune responses than schedule-A (three injections with 2-weeks interval). We showed that diphtheria toxoid can be successfully employed as a carrier protein for conjugation with Salmonella OSP and play an important role in facilitating adequate immune response.