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 mm² in the MVA group and 76.0 mm² 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<0.001).

Conclusions

No safety concerns associated with the MVA vaccine were identified. Immune responses and attenuation of the major cutaneous reaction suggest that this MVA vaccine protected against variola infection. (Funded by the Office of the Assistant Secretary for Preparedness and Response Biomedical Advanced Research and Development Authority of the Department of Health and Human Services and Bavarian Nordic; ClinicalTrials.gov number, NCT01913353.)

QUICK TAKE VIDEO SUMMARY
A Modified Smallpox Vaccine
02:15

中文翻译：

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改良痘苗安卡拉作为天花疫苗的三阶段功效试验

背景

由于担心天花再次出现，许多国家都储备了疫苗。传统的天花疫苗是基于复制型牛痘病毒。这些疫苗有相当大的副作用。

方法

为了评估改良牛痘安卡拉（MVA）作为潜在天花疫苗的功效，我们随机分配440名参与者接受两剂MVA，然后接受一剂已建立的复制牛痘疫苗ACAM2000（MVA组）或接受一剂ACAM2000（仅ACAM2000组）的名称。两个主要终点是就最大血清中和抗体滴度而言，MVA疫苗相对于ACAM2000的劣势，以及根据最大病变面积和推导面积衰减率测量的先前MVA疫苗对ACAM2000相关的主要皮肤反应的减弱。 。

结果

在MVA组和仅ACAM2000组中，分别有220和213名参与者被随机分配并接种了疫苗，并且208名参与者接受了两次MVA疫苗接种。在高峰访视时，MVA疫苗接种后第6周的几何平均效价为153.5，而使用ACAM2000的第4周的中位抗体的几何平均效价为79.3（比率为1.94 [95％置信区间{CI}，1.56至2.40]）。在第14天，单次MVA疫苗诱导的中和抗体的几何平均滴度（16.2）与ACAM2000诱导的中和抗体的几何平均滴度（16.2）相同，血清转化参与者的百分比相似（分别为90.8％和91.8％）。MVA组主要皮肤反应的中位病变面积为0 mm ²和76.0 mm ²仅使用ACAM2000的用户，其面积衰减率为97.9％（95％CI，96.6至98.3）。与仅使用ACAM2000的组相比，MVA组在两个MVA疫苗接种期后发生的不良事件或3级或更高的不良事件更少（17例与64名参与者的3级或更高的不良事件，P <0.001）。

结论

没有发现与MVA疫苗相关的安全隐患。免疫反应和主要皮肤反应的减弱表明，这种MVA疫苗可预防天花感染。（由卫生和公共服务部防备和响应生物医学高级研究与发展管理局助理秘书办公室和巴伐利亚北欧基金会资助； ClinicalTrials.gov编号，NCT01913353。）

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改良的天花疫苗
02:15