Safety and effectiveness of MVA-BN vaccination against mpox in at-risk individuals in Germany (SEMVAc and TEMVAc): a combined prospective and retrospective cohort study

IF 36.4 1区医学 Q1 INFECTIOUS DISEASES

Lancet Infectious Diseases Pub Date : 2025-03-18 DOI:10.1016/s1473-3099(25)00018-0

David Hillus, Ngoc Han Le, Pinkus Tober-Lau, Anne-Katrin Fietz, Christian Hoffmann, Regina Stegherr, Leu Huang, Axel Baumgarten, Florian Voit, Markus Bickel, Gal Goldstein, Christoph Wyen, Hartmut Stocker, Thomas Wünsche, Marcel Lee, Hubert Schulbin, Mathias Vallée, Ulrich Bohr, Anja Potthoff, Christiane Cordes, Leif Erik Sander

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引用次数: 0

Abstract

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.

查看原文本刊更多论文

德国高危人群（SEMVAc和TEMVAc）接种MVA-BN抗m痘疫苗的安全性和有效性：一项前瞻性和回顾性联合队列研究

背景自2022年全球暴发以来，已确认了11.5万多例麻疹病例。除了II支猴痘病毒（MPXV）的全球传播外，最近I支的传播已引起国际关注的突发公共卫生事件。第三代改良安卡拉-巴伐利亚北欧牛痘疫苗（MVA-BN）在2022年被推荐用于高危人群，尽管缺乏关于m痘安全性和有效性的数据。方法：我们在2022年7月7日至2023年12月31日期间，在德国进行了一项前瞻性、多中心、观察性研究（MVA-BN vaccine Against MPXV Infection [SEMVAc]的安全性和有效性），招募了18岁及以上的男男性行为者和变性人，评估了一剂和两剂皮下MVA-BN的安全性和反应原性。在一项模拟回顾性目标试验（MVA-BN疫苗预防高危人群m痘感染[TEMVAc]有效性模拟目标试验）中，使用Kaplan-Meier估计的风险比估计疫苗有效性，该模拟目标试验来自3027名接种疫苗的个体（1:1）和3027名未接种疫苗的对照组。SEMVAc和TEMVAc已在HMA-EMA目录（EUPAS50093）和德国临床试验注册（DRKS00029638）中注册，并且已经完成。结果：6459名个体被纳入SEMVAc前瞻性研究。不良反应很少（第一次剂量：0.35% [95% CI 0.20 - 0.60]，第二次剂量：0.14%[0.06 - 0.33]）。与第二次给药（56.8%[54.6 - 59]）相比，第一次给药后局部反应更频繁（70.2% [95% CI 68.5 - 71.8]），全身反应也更频繁（首次给药，22.3% [95% CI 20.9 - 23.9]）；第二次剂量，17.6%[15.9 - 19.4])。在TEMVAc，接种疫苗的个体报告了16例m痘病例，而匹配的未接种疫苗的个体报告了32例m痘病例（中位随访55天[IQR 23-89]）。一次剂量后14天或更晚的有效性总体为57.8% (95% CI 11.8 ~ 83.0)，未感染艾滋病毒者为84.1%(42.0 ~ 100)，而感染艾滋病毒者为34.9%（- 72.8 ~ 79.0）。与未接种疫苗的个体感染相比，突破性感染与症状减轻有关。mva - bn疫苗接种安全且耐受性良好。一剂MVA-BN可以预防m痘，但对艾滋病毒感染者的有效性降低。尽管随机对照试验仍然是评估疫苗效力的首选方法，但在动态的突发公共卫生事件中，结合前瞻性和回顾性研究设计可能是有价值的。资助欧洲药品管理局。摘要的德文译本见补充资料部分。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Lancet Infectious Diseases 医学-传染病学

CiteScore

60.90

自引率

0.70%

发文量

1064

审稿时长

6-12 weeks

期刊介绍： The Lancet Infectious Diseases was launched in August, 2001, and is a lively monthly journal of original research, review, opinion, and news covering international issues relevant to clinical infectious diseases specialists worldwide.The infectious diseases journal aims to be a world-leading publication, featuring original research that advocates change or sheds light on clinical practices related to infectious diseases. The journal prioritizes articles with the potential to impact clinical practice or influence perspectives. Content covers a wide range of topics, including anti-infective therapy and immunization, bacterial, viral, fungal, and parasitic infections, emerging infectious diseases, HIV/AIDS, malaria, tuberculosis, mycobacterial infections, infection control, infectious diseases epidemiology, neglected tropical diseases, and travel medicine. Informative reviews on any subject linked to infectious diseases and human health are also welcomed.