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改良安卡拉痘苗可有效预防天花
作者:小柯机器人 发布时间:2019/11/16 12:42:11

丹麦Bavarian Nordic公司的Paul Chaplin团队最近进行了一项改良的安卡拉痘苗作为天花疫苗的3期疗效试验。该研究于2019年11月14日发表于国际一流学术期刊《新英格兰医学杂志》上。

由于担心天花再次流行,许多国家都储存了疫苗。传统的天花疫苗基于复制的痘苗病毒,具有相当大的副作用。

为了评估改良的安卡拉痘苗(MVA)作为一种潜在天花疫苗的功效,研究组招募了433名受试者,将其随机分组,其中220名接受两剂MVA + 1剂现有的复制痘苗(ACAM2000),213名仅接受1剂ACAM2000。

MVA组中有208名受试者接受了两次MVA接种。高峰随访期,MVA疫苗在第6周诱导的中和抗体几何平均滴度为153.5,ACAM2000疫苗在第4周时为79.3。第14天,单剂MVA疫苗诱导的中和抗体几何平均滴度与ACAM2000疫苗相等,均为16.2,血清转化率也相差不大。MVA组未发生任何皮肤病变,仅ACAM2000组皮肤反应的平均病变面积为76mm2,面积衰减率为97.9%。MVA组在接受两剂MVA疫苗后不良事件和3级及以上严重不良事件的发生率显著低于仅ACAM2000组。

总之,未发现与MVA疫苗相关的安全问题。接种者的免疫反应和弱皮肤反应均表明,MVA疫苗可有效预防天花感染。

附:英文原文

Title: Phase 3 Efficacy Trial of Modified Vaccinia Ankara as a Vaccine against Smallpox

Author: Phillip R. Pittman, M.D.,, Matthew Hahn, M.D.,, HeeChoon S. Lee, M.D.,, Craig Koca, M.D.,, Nathaly Samy, M.D.,, Darja Schmidt, Ph.D.,, Joachim Hornung,, Heinz Weidenthaler, M.D.,, Christopher R. Heery, M.D.,, Thomas P.H. Meyer, Ph.D.,, Günter Silbernagl, M.Sc.,, Jane Maclennan, B.Sc.,, and Paul Chaplin, Ph.D.

Issue&Volume: 2019-11-13

Abstract:

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.

DOI: NJ201911143812005

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1817307

 

期刊信息

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于美国麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home