Vaccine Development Section, International Vaccine Institute, SNU Research Park, San 4-8, Nakseongdae-dong, Gwanak-gu 151-919, Seoul, Republic of Korea.
Vaccine. 2012 Feb 1;30(6):1023-8. doi: 10.1016/j.vaccine.2011.12.046. Epub 2011 Dec 20.
The influence pre-exposure of mice to Vi capsular polysaccharide, purified from Salmonella enterica Serovar Typhi, on the subsequent immune response induced by a Vi-diphtheria toxoid (Vi-DT) conjugate was evaluated. Vi induced low anti Vi IgG titers with the dominant subclass being IgG3. The Vi-DT conjugate induced high titers of anti Vi IgG with the dominant subclass being IgG1 but with considerable quantities of IgG2a, IgG2b and IgG3. Priming of mice with Vi suppressed the response to a subsequent dose of conjugate and the suppression was overcome by a second dose of conjugate. Priming with conjugate prevented suppression of the anti Vi response and subsequent dosing with Vi raised titers back to previous levels but did not boost to new higher levels. The anti DT IgG response to one dose of conjugate was relatively strong and protracted and continued to rise for 12 weeks, compared to the response to one dose of DT which was poor and peaked at two weeks. The prolonged anti DT response was most likely due to the slow release of DT from the conjugate lattice as it degrades within the mouse resulting in a continuous stimulation of the immune response. The presence of increasing amounts of un-conjugated Vi, up to 50%, administered with the conjugate resulted in increasingly higher levels of both anti Vi and anti DT. Larger amounts of un-conjugated Vi inhibited the anti Vi response. These findings have implications for vaccine quality and a limit for un-conjugated polysaccharide should not exceed 50% and from a vaccine program perspective if the results presented here translate to humans then a Vi conjugate, once it becomes available, should replace Vi polysaccharide vaccines.
预先给小鼠暴露于从伤寒沙门氏菌血清型 Typhi 中提取的 Vi 荚膜多糖，评估其对随后由 Vi-白喉类毒素（Vi-DT）缀合物诱导的免疫反应的影响。Vi 诱导低水平的抗 Vi IgG 滴度，主要亚类是 IgG3。Vi-DT 缀合物诱导高水平的抗 Vi IgG，主要亚类是 IgG1，但有相当数量的 IgG2a、IgG2b 和 IgG3。用 Vi 对小鼠进行初免会抑制对随后剂量的缀合物的反应，而通过第二剂量的缀合物可以克服抑制。用缀合物进行初免可防止对 Vi 反应的抑制，随后用 Vi 给药可使抗体滴度恢复到以前的水平，但不会提高到新的更高水平。单次接种缀合物的抗 DT IgG 反应相对较强且持久，持续升高 12 周，而单次接种 DT 的反应较弱，在两周时达到峰值。与单次接种 DT 相比，这种延长的抗 DT 反应很可能是由于 DT 从缀合物晶格中缓慢释放，因为它在小鼠体内降解，导致免疫反应持续受到刺激。与缀合物一起给予的未缀合的 Vi 量增加（高达 50%）会导致抗 Vi 和抗 DT 水平均升高。更多的未缀合的 Vi 抑制抗 Vi 反应。这些发现对疫苗质量有影响，并且缀合的多糖不应超过 50%。从疫苗计划的角度来看，如果这里提出的结果转化为人类，那么一旦可用，Vi 缀合物应该替代 Vi 多糖疫苗。
