Immune suppression induced by Vi capsular polysaccharide is overcome by Vi-DT conjugate vaccine
Immune suppression induced by Vi capsular polysaccharide is overcome by Vi-DT conjugate vaccine
复制标题
DOI：
10.1016/j.vaccine.2011.12.046
复制
发表时间：
2012-02-01
期刊：
影响因子：
5.5
通讯作者：
Carbis, Rodney
中科院分区：
文献类型：
--
作者：
An, So Jung;Yoon, Yeon Kyung;Carbis, Rodney
本研究评估了小鼠预先暴露于从伤寒沙门氏菌中纯化的Vi荚膜多糖对随后由Vi-白喉类毒素（Vi- dt）偶联物诱导的免疫应答的影响。Vi诱导低抗Vi IgG滴度，优势亚类为IgG3。Vi- dt偶联物诱导高滴度的抗Vi IgG，主要亚类为IgG1，但也含有相当数量的IgG2a、IgG2b和IgG3。用Vi启动小鼠抑制了对随后剂量的偶联物的反应，这种抑制被第二剂量的偶联物所克服。用共轭物启动防止了抗Vi反应的抑制，随后的Vi剂量将滴度提高到以前的水平，但没有提高到新的更高水平。一剂偶联剂的抗DT IgG应答较强，持续时间较长，持续上升12周，而一剂DT的应答较差，在2周达到峰值。延长的抗DT反应很可能是由于DT从共轭晶格缓慢释放，因为它在小鼠体内降解，导致免疫反应的持续刺激。随着偶联物的存在，未偶联的Vi的数量增加，高达50%，导致抗Vi和抗DT的水平越来越高。大量的未共轭的维抑制抗维反应。这些发现对疫苗质量有影响，未偶联多糖的限制不应超过50%，从疫苗计划的角度来看，如果这里的结果转化为人类，那么一旦有了Vi偶联物，就应该取代Vi多糖疫苗。(C) 2011 Elsevier Ltd.版权所有。
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. (C) 2011 Elsevier Ltd. All rights reserved.