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
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, M. Vallée, Ulrich Bohr, Anja Potthoff, Christiane Cordes, Caroline Isner, Bethany Knox, Antonio Losa Carmona, N. Stobäus, Ran D. Balicer, Axel Adam, Yvonne Ahlgrimm, Sebastian Albus, Maher Almahfoud, Christina Appelhans, Sergio Bassano, Daniel Beer, Christoph Boesecke, Jan Borch, Marcos Vinicius de Oliveira Gouvêa, Olaf Degen, Nicolas Deltour, Lars Esmann, Stefan Esser, Stefan Fenske, Josephine Fink, Ulrike Föllmer, Andre Fuchs, Elisabeth Garry, Nicole Gersbacher-Runge, Stefan Grunwald, Anja Hagemann, Janina Hammer, Stefan Hansen, Andreas Hetey, Anna Hiller, Alexandra Hofmann, Klaus Jansen, Stefanie Jentzsch, Ulrich Kastenbauer, Angela Klingmüller, Heribert Knechten, Henning Kolarikal, Jenny Kollek, Tim Kümmerle, Kerstin Lammersmann, Clara Lehmann, Florentina Leitner, Vladislav Leshchinskiy, Michelle Lisy, Constantin Loers, Niklas Lund, Constanze Lüttke, Thomas Lutz, Felix Maischack, Nicolai Menner, Oskars Mikazans, Malte Benedikt Monin, Isabel Mordhorst, Janina Motsch, Parnika Mukherjee, Marius Müller, Sebastian Noe, Amanda Oliveira, Hanaya Raad, Pascale Ricardoni, Katharina Richter, Jürgen Rockstroh, Nicolas Marcel Roth, Ines Ruck, Stefanie Sammet, Guido Schäfer, Michael Scheer, Pia Schenk-Westkamp, Knud Schewe, Angelika Schliephake, Stephan Schneeweiß, Jochen Schneider, Stefan Scholten, Reinhold Schröder, Christoph Schuler, Saskia Schwalgun, Georg Schwanitz, Richard Sinzig, Miriam Speer
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.