Hillus David, Le Ngoc Han, Tober-Lau Pinkus, Fietz Anne-Katrin, Hoffmann Christian, Stegherr Regina, Huang Leu, Baumgarten Axel, Voit Florian, Bickel Markus, Goldstein Gal, Wyen Christoph, Stocker Hartmut, Wünsche Thomas, Lee Marcel, Schulbin Hubert, Vallée Mathias, Bohr Ulrich, Potthoff Anja, Cordes Christiane, Isner Caroline, Knox Bethany, Carmona Antonio, Stobäus Nicole, Balicer Ran, Kurth Florian, Sander Leif Erik
Department of Infectious Diseases and Critical Care Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Institute of Biometry and Clinical Epidemiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Lancet Infect Dis. 2025 Jul;25(7):775-787. doi: 10.1016/S1473-3099(25)00018-0. Epub 2025 Mar 18.
BACKGROUND: More than 115 000 cases of mpox have been confirmed since the onset of a global outbreak in 2022. In addition to global transmission of clade II monkeypox virus (MPXV), the recent spread of clade I has caused a Public Health Emergency of International Concern. The third-generation smallpox vaccine modified vaccinia Ankara-Bavarian Nordic (MVA-BN) was recommended for at-risk populations in 2022, despite a scarcity of data on safety and effectiveness against mpox. METHODS: We did a prospective, multicentre, observational study, enrolling men who have sex with men and transgender people aged 18 years or older with changing sexual partners in Germany (Safety and Effectiveness of MVA-BN Vaccination Against MPXV Infection [SEMVAc]) between July 7, 2022, and Dec 31, 2023, evaluating safety and reactogenicity of one and two doses of subcutaneous MVA-BN. Vaccine effectiveness was estimated using risk ratios from the Kaplan-Meier estimator in an emulated retrospective target trial (Emulated Target Trial for Effectiveness of MVA-BN Vaccination Against mpox Infection in At-risk Individuals [TEMVAc]) from 3027 vaccinated individuals matched (1:1) to 3027 unvaccinated controls. SEMVAc and TEMVAc were registered in the HMA-EMA Catalogue, EUPAS50093, and the German Clinical Trials Register, DRKS00029638, and are complete. FINDINGS: 6459 individuals were prospectively enrolled in SEMVAc. Adverse reactions were infrequent (first dose: 0·35% [95% CI 0·20-0·60] and second dose: 0·14% [0·06-0·33]). Local reactions were more frequent after the first dose (70·2% [95% CI 68·5-71·8]) compared with the second dose (56·8% [54·6-59]), as were systemic reactions (first dose, 22·3% [95% CI 20·9-23·9]; second dose, 17·6% [15·9-19·4]). In TEMVAc, 16 mpox cases were reported in vaccinated individuals versus 32 cases in matched unvaccinated individuals (median follow-up 55 days [IQR 23-89]). Effectiveness by 14 days or later after one dose was 57·8% (95% CI 11·8 to 83·0) overall, 84·1% (42·0 to 100) in people without HIV, but 34·9% (-72·8 to 79·0) in people living with HIV. Breakthrough infections were associated with reduced symptoms, compared with infections in unvaccinated individuals. INTERPRETATION: MVA-BN vaccination was safe and well tolerated. One dose of MVA-BN offered protection against mpox but effectiveness was reduced in people living with HIV. Although randomised controlled trials remain the preferred approach for assessing vaccine efficacy, combining prospective and retrospective study designs can be valuable during dynamic public health emergencies. FUNDING: European Medicines Agency. TRANSLATION: For the German translation of the abstract see Supplementary Materials section.
背景：自2022年全球猴痘疫情爆发以来，已确诊超过11.5万例猴痘病例。除了II型分支猴痘病毒（MPXV）的全球传播外，I型分支的近期传播已引发国际关注的突发公共卫生事件。尽管针对猴痘的安全性和有效性数据稀缺，但2022年仍建议为高危人群接种第三代天花疫苗——安卡拉痘苗病毒-巴伐利亚北欧株（MVA-BN）。 方法：我们开展了一项前瞻性、多中心观察性研究，纳入2022年7月7日至2023年12月31日期间在德国有多个性伴侣的18岁及以上男男性行为者和跨性别者（MVA-BN疫苗接种预防MPXV感染的安全性和有效性[SEMVAc]），评估单剂量和双剂量皮下注射MVA-BN的安全性和反应原性。在一项模拟回顾性目标试验（高危个体中MVA-BN疫苗接种预防猴痘感染有效性的模拟目标试验[TEMVAc]）中，使用来自Kaplan-Meier估计量的风险比，对3027名接种疫苗个体（与未接种疫苗的3027名对照个体1:1匹配）的疫苗有效性进行估计。SEMVAc和TEMVAc已在HMA-EMA目录（EUPAS50093）和德国临床试验注册库（DRKS00029638）中注册，且研究已完成。 结果：6459名个体前瞻性纳入SEMVAc。不良反应发生率较低（第一剂：0.35%[95%CI 0.20 - 0.60]，第二剂：0.14%[0.06 - 0.33]）。与第二剂（56.8%[54.6 - 59]）相比，第一剂后的局部反应更常见（70.2%[95%CI 68.5 - 71.8]），全身反应也是如此（第一剂，22.3%[95%CI 20.9 - 23.9]；第二剂，17.6%[15.9 - 19.4]）。在TEMVAc中，接种疫苗个体报告了16例猴痘病例，而匹配的未接种疫苗个体中有32例（中位随访55天[IQR 23 - 89]）。一剂接种后14天及以后的总体有效性为57.8%（95%CI 11.8至83.0），未感染HIV者为84.1%（42.0至100），但感染HIV者为34.9%（-72.8至79.0）。与未接种疫苗个体的感染相比，突破性感染的症状较轻。 解读：MVA-BN疫苗接种安全且耐受性良好。单剂量MVA-BN可提供针对猴痘的保护，但感染HIV者的有效性降低。尽管随机对照试验仍是评估疫苗疗效的首选方法，但在动态公共卫生紧急事件期间，将前瞻性和回顾性研究设计相结合可能很有价值。 资助：欧洲药品管理局。 译文：摘要的德语翻译见补充材料部分。
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