Varicella vaccination: Evidence for frequent reactivation of the vaccine strain in healthy children
Varicella vaccination: Evidence for frequent reactivation of the vaccine strain in healthy children
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DOI：
10.1038/74715
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发表时间：
2000-04-01
期刊：
影响因子：
82.9
通讯作者：
Klinman, DM
中科院分区：
文献类型：
--
作者：
Krause, PR;Klinman, DM
野生型水痘试验病毒（VZV）引起水痘，这是一种常见的儿童疾病，其特征是发烧和水泡性皮疹（1）以及罕见的严重并发症。野生型VZV在感觉神经节中以潜伏形式存在，并可重新激活以引起带状疱疹（3）。自1995年获得许可以来，已有1000多万美国儿童接种了Oka株VZV减毒活疫苗（OkaVZV）。许可证前的临床研究表明，接种疫苗者的平均血清抗VZV水平在接种疫苗后随时间持续增加。这是由于在社区中暴露于野生型VZV引起的免疫增强（4，5）。在这里，我们研究了另一种选择，即大规模无症状的OkaVZV再激活可能发生在疫苗接种者中。我们分析了4，631名OkaVZV免疫儿童4年随访的血清抗体水平和感染率。抗VZV滴度随着时间的推移在高应答受试者中下降，但在低滴度的疫苗接种者中上升。在抗VZV滴度低的受试者中，临床感染和免疫增强的频率大大超过了每年13%的野生型水痘暴露率。这些发现表明OkaVZV在体内持续存在，并且在接种后随着血清抗体滴度降低而重新活化。这对于用OkaVZV免疫的个体具有显著的后果。
Wild-type varicella tester virus (VZV) causes chickenpox, a common childhood illness characterized by fever and a vesicular rash(1) and rare serious complications'. Wild-type VZV persists in a latent form in the sensory ganglia, and can re-activate to cause herpes zoster(3). More than 10 million American children have received the live attenuated Oka strain VZV vaccine (OkaVZV) since its licensure in 1995. Pre-licensure clinical studies showed that mean serum anti-VZV levels among vaccinees continued to increase with time after vaccination. This was attributed to immunologic boosting caused by exposure to wild-type VZV in the community(4,5). Here, we examine the alternative, that large-scale asymptomatic reactivation of OkaVZV might occur in vaccinees. We analyzed serum antibody levels and infection rates for 4 years of follow-up in 4,631 children immunized with OkaVZV. Anti-VZV titers decreased over time in high-responder subjects, but rose in vaccinees with low titers. Among subjects with low anti-VZV titers, the frequency of clinical infection and immunological boosting substantially exceeded the 13%-per-year rate of exposure to wild-type varicella. These findings indicate that OkaVZV persisted in vivo and reactivated as serum antibody titers decreased after vaccination. This has salient consequences for individuals immunized with OkaVZV.