A Phase I Trial of Epstein-Barr Virus Gp350 Vaccine for Children With Chronic Kidney Disease Awaiting Transplantation
A Phase I Trial of Epstein-Barr Virus Gp350 Vaccine for Children With Chronic Kidney Disease Awaiting Transplantation
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DOI：
10.1097/tp.0b013e3181b9d918
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发表时间：
2009-10-27
期刊：
影响因子：
6.2
通讯作者：
Steven, Neil M.
中科院分区：
文献类型：
--
作者：
Rees, Lesley;Tizard, E. Jane;Steven, Neil M.
背景。接种eb病毒（EBV）疫苗，诱导对包膜糖蛋白gp350的抗体反应，可能保护EBV阴性的慢性肾脏疾病儿童在移植后免受淋巴增生性疾病的侵袭。一项I期试验招募了患有慢性肾脏疾病的儿童，分为两个连续队列，在6至8周的时间内分别注射12.5 μ g （n=6）和25 μ g （n=10）重组gp350/醛水凝胶疫苗。在第28周评估前，每个队列中有1人获得野生EBV。两种剂量的免疫原性相似，在所有13名可评估的患者中诱导IgG反应。在4名受者中检测到中和抗体（12.5 μ g组中1/4,25 μ g组中3/9）。从首次接种疫苗到移植的中位时间为24周。免疫反应迅速下降，不太可能影响移植后的事件。该疫苗具有免疫原性，但在未来的试验中，需要延长疫苗接种时间，直到移植时或改进佐剂，以减少移植后EBV载量和淋巴增生性疾病的风险。
Background. Vaccination against Epstein-Barr virus (EBV), inducing an antibody response to the envelope glycoprotein gp350, might protect EBV-negative children with chronic kidney disease from lymphoproliferative disease after transplantation.Methods. A phase I trial recruited children with chronic kidney disease to two successive cohorts given three injections of 12.5 mu g (n=6) and 25 mu g (n=10) recombinant gp350/alhydrogel vaccine over 6 to 8 weeks.Results. One in each cohort acquired wild EBV before the week 28 evaluation. Both doses were similarly immunogenic, inducing an IgG response in all 13 evaluable patients. Neutralizing antibodies were detected in four recipients (1/4 in the 12.5 mu g and 3/9 in the 25 mu g cohort). Median time from first vaccination to transplantation was 24 weeks. Immune responses declined rapidly and were unlikely to affect posttransplant events.Discussion. The vaccine was immunogenic but a prolonged vaccine schedule up to time of transplantation or improved adjuvants are required in future trials to reduce posttransplant EBV load and risk of lymphoproliferative disease.