A Randomized, Controlled Trial of an Aerosolized Vaccine against Measles
A Randomized, Controlled Trial of an Aerosolized Vaccine against Measles
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DOI：
10.1056/nejmoa1407417
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发表时间：
2015-04-16
影响因子：
158.5
通讯作者：
Restrepo, A. M. Henao
中科院分区：
文献类型：
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作者：
Low, N.;Bavdekar, A.;Restrepo, A. M. Henao
背景疫苗可作为一种针对麻疹的无针免疫方法，麻疹是一种仍然是疾病和死亡的主要原因。关于麻疹雾化疫苗在儿童中的免疫原性的数据是不一致的。方法我们在印度进行了一项开放标签的非劣性试验，对象为9.0至11.9个月的儿童，他们有资格接种第一剂麻疹疫苗。儿童被随机分配以雾化吸入或皮下注射的方式接受单剂疫苗接种。主要终点是接种疫苗91天后麻疹抗体的血清阳性和不良事件。结果共有1001名儿童被分配接种雾化疫苗，1003名儿童被分配接受皮下疫苗接种，1956名儿童(97.6%)被跟踪到第91天，但331名儿童因标本解冻而未能获得结果数据。在按方案进行的人群中，可以对2004年1560名儿童(77.8%)的数据进行评估。在第91天，气雾剂组775名儿童中662名(85.4%；95%可信区间82.5-88.0)与皮下注射组785名儿童中743名(94.6%；95%CI，92.7-96.1)血清阳性，差异-9.2个百分点(95%CI，-12.2-6.3)。全分析组的结果类似(气雾组788名儿童中的673名[85.4%]和皮下组796名儿童中的754名[94.7%]在第91天血清阳性，差异-9.3个百分点[95%CI，-12.3至-6.4])，并多次归因于丢失的结果。没有任何严重不良事件可归因于接种麻疹疫苗。两组的不良事件情况相似。结论麻疹雾化疫苗具有免疫原性，但在规定的范围内，雾化疫苗的血清阳性率低于皮下疫苗。
BACKGROUNDAerosolized vaccine can be used as a needle-free method of immunization against measles, a disease that remains a major cause of illness and death. Data on the immunogenicity of aerosolized vaccine against measles in children are inconsistent.METHODSWe conducted an open-label noninferiority trial involving children 9.0 to 11.9 months of age in India who were eligible to receive a first dose of measles vaccine. Children were randomly assigned to receive a single dose of vaccine by means of either aerosol inhalation or a subcutaneous injection. The primary end points were seropositivity for antibodies against measles and adverse events 91 days after vaccination. The noninferiority margin was 5 percentage points.RESULTSA total of 1001 children were assigned to receive aerosolized vaccine, and 1003 children were assigned to receive subcutaneous vaccine; 1956 of all the children (97.6%) were followed to day 91, but outcome data were missing for 331 children because of thawed specimens. In the per-protocol population, data on 1560 of 2004 children (77.8%) could be evaluated. At day 91, a total of 662 of 775 children (85.4%; 95% confidence interval [CI], 82.5 to 88.0) in the aerosol group, as compared with 743 of 785 children (94.6%; 95% CI, 92.7 to 96.1) in the subcutaneous group, were seropositive, a difference of -9.2 percentage points (95% CI, -12.2 to -6.3). Findings were similar in the full-analysis set (673 of 788 children in the aerosol group [85.4%] and 754 of 796 children in the subcutaneous group [94.7%] were seropositive at day 91, a difference of -9.3 percentage points [95% CI, -12.3 to -6.4]) and after multiple imputation of missing results. No serious adverse events were attributable to measles vaccination. Adverse-event profiles were similar in the two groups.CONCLUSIONSAerosolized vaccine against measles was immunogenic, but, at the prespecified margin, the aerosolized vaccine was inferior to the subcutaneous vaccine with respect to the rate of seropositivity.