MassBiologics, University of Massachusetts Medical School, Boston, MA, USA.
Vaccine. 2010 Jan 22;28(4):965-9. doi: 10.1016/j.vaccine.2009.10.144. Epub 2009 Nov 24.
Previous studies have demonstrated a correlation between Clostridium difficile anti-toxin A serum antibodies and protection against symptomatic disease and recurrence.
A neutralizing monoclonal antibody to C. difficile toxin A (CDA1) developed by MBL and Medarex, Inc. was studied in a phase II, randomized, double-blind, placebo-controlled trial in patients receiving standard of care treatment for C. difficile infection (CDI). Twenty-nine subjects received a single intravenous infusion of 10mg/kg CDA1 and 17 subjects received placebo and were evaluated for recurrence of CDI during the 56-day study period. Serum antibodies against C. difficile toxin A and B were measured by ELISA and cytotoxicity assay at various time points before and after infusion.
CDI recurrence occurred in 5 of 29 (17%) in the CDA1 group and 3 of 17 (18%) (p=NS) in the placebo group with a trend toward delay in time to recurrence in the group treated with CDA1. The geometric mean concentration of antibody to an epitope of the receptor-binding domain of toxin B (0.300 and 1.20microg/ml, respectively; p=0.02) and geometric mean titer of neutralizing B antibody (8.00 and 100, respectively; p=0.02) at study day 28 were lower for those subjects with recurrence compared to those who did not recur. In addition, a significantly greater proportion of subjects who recurred were infected with the epidemic BI/NAP1/027 strain compared with those that did not recur (88% vs. 22%; p=0.002). Finally, in a multiple logistic regression analysis neutralizing anti-toxin B at day 14 (p<0.001), anti-toxin A at day 28 (p<0.001) and infection with the BI/NAP1/027 strain at enrollment (p=0.002) were all predictive of CDI recurrence.
In this prospective study, lower concentrations of neutralizing anti-toxin B and anti-toxin A antibody and infection with the BI/NAP1/027 strain of C. difficile were significantly associated with recurrence of CDI.
先前的研究表明，艰难梭菌抗毒素 A 血清抗体与预防有症状疾病和复发之间存在相关性。
由 MBL 和 Medarex 公司开发的一种针对艰难梭菌毒素 A（CDA1）的中和单克隆抗体在一项接受标准治疗的艰难梭菌感染（CDI）患者的 II 期、随机、双盲、安慰剂对照试验中进行了研究。29 名受试者接受了单次静脉输注 10mg/kg CDA1，17 名受试者接受了安慰剂，并在 56 天的研究期间评估了 CDI 的复发情况。在输注前后的不同时间点通过 ELISA 和细胞毒性测定法测量针对艰难梭菌毒素 A 和 B 的血清抗体。
CDA1 组中有 5 例（17%）复发，安慰剂组中有 3 例（18%）（p=NS），CDA1 治疗组的复发时间有延迟趋势。与未复发的患者相比，复发患者针对毒素 B 受体结合域表位的抗体的几何平均浓度（分别为 0.300 和 1.20μg/ml；p=0.02）和中和 B 抗体的几何平均效价（分别为 8.00 和 100；p=0.02）在研究第 28 天均较低。此外，与未复发的患者相比，复发患者中有更大比例的患者感染了流行的 BI/NAP1/027 株（88% vs. 22%；p=0.002）。最后，在多变量逻辑回归分析中，第 14 天的中和抗毒素 B（p<0.001）、第 28 天的抗毒素 A（p<0.001）和入组时感染 BI/NAP1/027 株（p=0.002）均与 CDI 复发相关。
在这项前瞻性研究中，中和抗毒素 B 和抗毒素 A 抗体的浓度较低以及感染 BI/NAP1/027 型艰难梭菌与 CDI 的复发显著相关。
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