First Human Challenge Testing of a Pneumococcal Vaccine Double-Blind Randomized Controlled Trial
First Human Challenge Testing of a Pneumococcal Vaccine Double-Blind Randomized Controlled Trial
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DOI：
10.1164/rccm.201503-0542oc
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发表时间：
2015-10-01
影响因子：
24.7
通讯作者：
Gordon, Stephen B.
中科院分区：
文献类型：
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作者：
Collins, Andrea M.;Wright, Angela D.;Gordon, Stephen B.
理由：迫切需要新的疫苗来保护易受感染的人免受细菌性肺炎的伤害。肺炎疫苗的临床试验既缓慢又昂贵，需要数万名患者。肺炎球菌疫苗抗定植效果的研究被认为是一种在候选疫苗中进行筛选的新方法。目的：利用我们安全、可重复性的实验性人肺炎球菌定植模型，研究13价肺炎球菌结合疫苗(PCV)对定植的影响。方法：100名年龄在18-50岁的健康受试者参加这项双盲随机安慰剂对照试验。随机分为卡介苗接种组(n=49)和甲型肝炎疫苗对照组(n=50)，每滴鼻分别接种8万cfu/百亩L肺炎链球菌(6B)。PCV组的6B定植率(10%，5/481)显著低于对照组(48%，23/481)(风险比，0.22；可信区间，0.09~0.52；P<；0.001)。接种后PCV组的定植密度较对照组降低。与对照组相比，PCV的曲线下面积(密度-天)显著减小(几何平均值，259比11,183；P=0.017)。结论：PCV降低了健康成人肺炎球菌的定殖率、密度和持续时间。实验性人类肺炎球菌定植模型是一种安全、经济和有效的方法来确定新疫苗对肺炎球菌定植的保护效果；PCV提供了测试这些新型疫苗的金标准。
Rationale: New vaccines are urgently needed to protect the vulnerable from bacterial pneumonia. Clinical trials of pneumonia vaccines are slow and costly, requiring tens of thousands of patients. Studies of pneumococcal vaccine efficacy against colonization have been proposed as a novel method to down-select between vaccine candidates.Objectives: Using our safe and reproducible experimental human pneumococcal colonization model, we aimed to determine the effect of 13-valent pneumococcal conjugate vaccine (PCV) on colonization.Methods: A total of 100 healthy participants aged 18-50 years were recruited into this double-blind randomized placebo-controlled trial. They were randomly assigned to PCV (n = 49) or hepatitis A (control, n = 50) vaccination and inoculated with 80,000 CFU/100 mu l of Streptococcus pneumoniae (6B) per naris.Measurements and Main Results: Participants were followed up for 21 days to determine pneumococcal colonization by culture of nasal wash. The PCV group had a significantly reduced rate of 6B colonization (10% [5 of 481) compared with control subjects (48% [23 of 481) (risk ratio, 0.22; confidence interval, 0.09-0.52; P < 0.001). Density of colonization was reduced in the PCV group compared with the control group following inoculation. The area under the curve (density vs. day) was significantly reduced in the PCV compared with control group (geometric mean, 259 vs. 11,183; P = 0.017).Conclusions: PCV reduced pneumococcal colonization rate, density, and duration in healthy adults. The experimental human pneumococcal colonization model is a safe, cost-effective, and efficient method to determine the protective efficacy of new vaccines on pneumococcal colonization; PCV provides a gold standard against which to test these novel vaccines.