Phase 1 Study of the Safety and Immunogenicity of a Live, Attenuated Respiratory Syncytial Virus and Parainfluenza Virus Type 3 Vaccine in Seronegative Children
Phase 1 Study of the Safety and Immunogenicity of a Live, Attenuated Respiratory Syncytial Virus and Parainfluenza Virus Type 3 Vaccine in Seronegative Children
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DOI：
10.1097/inf.0b013e31823386f1
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发表时间：
2012-02-01
影响因子：
3.6
通讯作者：
Dubovsky, Filip
中科院分区：
文献类型：
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作者：
Bernstein, David I.;Malkin, Elissa;Dubovsky, Filip
背景：呼吸道合胞病毒(RSV)和副流感病毒3型(PIV3)是引起幼儿下呼吸道疾病和住院的重要原因。目前，还没有针对RSV或PIV3的特许疫苗。方法：在这项随机、第1阶段、双盲、安慰剂对照、剂量递增的研究中，49名6至24个月的健康RSV/PIV3血清阴性儿童被随机分为3剂(10(4)、10(5)或10(6)中位组织培养感染量[TCID(50)])或安慰剂，每隔2个月接受一次Medi-534(一种活的、减毒的RSV/PIV3嵌合病毒候选疫苗)或安慰剂。记录每次服药后0-28天的主动不良事件(SE)和主动不良事件(AEs)。在每次服药后和非计划就诊时，收集3次鼻腔冲洗样本(第7-10天、12-18天和28-34天)。在每次服药后28天和基线时采集血样进行抗体反应。结果：总的来说，RSV/PIV3疫苗组和安慰剂组的SE和AEs的发生率没有差异。流鼻水/鼻塞是最常见的SE报道。接受医疗护理的较低呼吸道疾患率在治疗部门之间保持平衡，没有证据表明RSV疾病或与疫苗相关的严重急性呼吸综合征。多数接种者在接种后第7~10天检测到疫苗病毒，且呈剂量依赖关系。在接受10(6)剂量的受试者中，对RSV和PIV3的血清应答最高。结论：在RSV/PIV3血清阴性的儿童人群中，通过脱落和/或血清反应测量的安全性和疫苗接种量支持这种RSV/PIV3儿科候选疫苗的继续发展。
Background: Respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3) are important causes of lower respiratory tract illness and hospitalization in young children. Currently, there is no licensed vaccine against RSV or PIV3.Methods: In this randomized, phase 1, double-blind, placebo-controlled, dose-escalating study, 49 healthy RSV/PIV3-seronegative children 6 to < 24 months of age were randomized 2: 1 to receive 3 doses (at 10(4), 10(5), or 10(6) median tissue culture infective dose [TCID(50)]) of MEDI-534 (a live, attenuated RSV/PIV3 chimeric virus vaccine candidate) or placebo at 2-month intervals. Solicited adverse events (SEs) and unsolicited adverse events (AEs) were recorded during days 0 to 28 after each dose. Nasal wash samples were collected 3 times (days 7-10, 12-18, and 28-34) after each dose and at unscheduled illness visits. Blood for antibody response was collected at baseline and 28 days after each dose. Subjects were followed for 180 days after the last dose or to the end of the RSV season.Results: Overall, there was no difference in the incidence of SEs and AEs between the RSV/PIV3 vaccine and placebo arms. Runny/stuffy nose was the most commonly reported SE. Medically attended lower respiratory illness rates were balanced between treatment arms, and there was no evidence of enhanced RSV disease or vaccine-related serious AEs. Vaccine virus was detected in most vaccinees on days 7 to 10 after dose 1 in a dose-dependent manner. Seroresponse to RSV and PIV3 was highest in subjects receiving the 10(6) dosage.Conclusions: The safety profile and vaccine take as measured by shedding and/or seroresponse in this RSV/PIV3-seronegative pediatric population support the continued development of this RSV/PIV3 pediatric vaccine candidate.