Phase 3 Efficacy Trial of Modified Vaccinia Ankara as a Vaccine against Smallpox
Phase 3 Efficacy Trial of Modified Vaccinia Ankara as a Vaccine against Smallpox
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DOI：
10.1056/nejmoa1817307
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发表时间：
2019-11-14
影响因子：
158.5
通讯作者：
Chaplin, Paul
中科院分区：
文献类型：
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作者：
Pittman, Phillip R.;Hahn, Matthew;Chaplin, Paul
背景由于担心天花卷土重来，许多国家都储备了疫苗。传统的天花疫苗是以复制牛痘病毒为基础的；这些疫苗有相当大的副作用。方法为评价改良安卡拉痘苗(MVA)作为一种潜在的天花疫苗的有效性，我们随机将440名参与者分成两组，分别接种两剂MVA和一剂已建立的复制疫苗ACAM2000(MVA组)或一剂ACAM2000疫苗(仅ACAM2000组)。两个主要终点是MVA疫苗相对于ACAM2000的血清中和抗体峰值滴度不低于ACAM2000，以及根据最大皮损面积和派生面积衰减率测量，先前接种MVA疫苗的ACAM2000相关主要皮肤反应减弱。结果MVA组和单纯ACAM2000组分别有220人和213人被随机分配接种，其中208人接种了两次MVA疫苗。在访问高峰时，接种MVA疫苗在第6周诱导的几何平均中和抗体滴度为153.5，而在ACAM2000接种的第4周诱导的中和抗体滴度为79.3%(比率为1.94[95%可信区间{CI}，1.5 6至2.40])。第14天，单次MVA疫苗诱导的中和抗体几何平均滴度(16.2)与ACAM2000诱导的中和抗体几何平均滴度(16.2)相当，血清转换率相似(分别为90.8%和91.8%)。MVA组和ACAM2000组主要皮肤反应的中位皮损面积分别为0 mm(2)和76.0 mm(2)，面积衰减率为97.9%(95%CI，96.6~98.3)。在两个MVA疫苗接种周期后，MVA组的不良事件或3级或更高级别的不良事件少于仅ACAM2000组(17名不良事件为3级或更高的参与者，P
Background Many countries have stockpiled vaccines because of concerns about the reemergence of smallpox. Traditional smallpox vaccines are based on replicating vaccinia viruses; these vaccines have considerable side effects. Methods To evaluate the efficacy of modified vaccinia Ankara (MVA) as a potential smallpox vaccine, we randomly assigned 440 participants to receive two doses of MVA followed by one dose of the established replicating-vaccinia vaccine ACAM2000 (the MVA group) or to receive one dose of ACAM2000 (the ACAM2000-only group). The two primary end points were noninferiority of the MVA vaccine to ACAM2000 with respect to the peak serum neutralizing antibody titers and attenuation of the ACAM2000-associated major cutaneous reaction by previous MVA vaccination, measured according to the maximum lesion area and the derived area attenuation ratio. Results A total of 220 and 213 participants were randomly assigned and vaccinated in the MVA group and ACAM2000-only group, respectively, and 208 participants received two MVA vaccinations. At peak visits, MVA vaccination induced a geometric mean titer of neutralizing antibodies of 153.5 at week 6, as compared with 79.3 at week 4 with ACAM2000 (a ratio of 1.94 [95% confidence interval {CI}, 1.56 to 2.40]). At day 14, the geometric mean titer of neutralizing antibodies induced by a single MVA vaccination (16.2) was equal to that induced by ACAM2000 (16.2), and the percentages of participants with seroconversion were similar (90.8% and 91.8%, respectively). The median lesion areas of the major cutaneous reaction were 0 mm(2) in the MVA group and 76.0 mm(2) in the ACAM2000-only group, resulting in an area attenuation ratio of 97.9% (95% CI, 96.6 to 98.3). There were fewer adverse events or adverse events of grade 3 or higher after both MVA vaccination periods in the MVA group than in the ACAM2000-only group (17 vs. 64 participants with adverse events of grade 3 or higher, P