Vaccine Development Section, Laboratory Sciences Division, International Vaccine Institute, Seoul, Republic of Korea.
Vaccine. 2011 Oct 13;29(44):7618-23. doi: 10.1016/j.vaccine.2011.08.019. Epub 2011 Aug 16.
In this study it was demonstrated that the immunogenicity of Vi polysaccharide-diphtheria toxoid conjugates was related to the physical and chemical structure of the conjugate. Conjugates were prepared in two steps, firstly binding adipic acid dihydrazide (ADH) spacer molecules to diphtheria toxoid (DT) carrier protein then secondly binding varying amounts of this derivatized DT to a fixed amount of Vi capsular polysaccharide purified from Salmonella enterica Serovar Typhi. As the amount of DT bound to the Vi increased the size of the conjugate increased but also the degree of cross-linking increased. The immunogenicity of the conjugates was tested in mice and measured by ELISA for anti Vi and anti DT IgG responses, and the results revealed a trend that as the amount of DT bound to the Vi increased the anti Vi responses increased. This study establishes a correlation between physico-chemical characteristics of the conjugate and the magnitude of the anti Vi and anti DT responses.
在这项研究中,证明了 Vi 多糖-白喉类毒素结合物的免疫原性与其结合物的物理化学结构有关。结合物通过两步制备,首先将己二酰二肼(ADH)间隔物分子结合到白喉类毒素(DT)载体蛋白上,然后将不同量的衍生化 DT 结合到从伤寒沙门氏菌血清 Typhi 中纯化的固定量的 Vi 荚膜多糖上。随着结合到 Vi 上的 DT 量增加,结合物的大小增加,但交联程度也增加。通过 ELISA 检测小鼠中的结合物的免疫原性,以测量抗 Vi 和抗 DT IgG 反应,结果显示,随着结合到 Vi 上的 DT 量增加,抗 Vi 反应增加。这项研究建立了结合物的物理化学特性与抗 Vi 和抗 DT 反应的大小之间的相关性。