c8aa8ac0ecd2ab98d93df064db9e1ca0 vaccines-13-00594-v2.pdf 36b4de6d7466ee9bde78a7d253065035b67eeaed vaccines-13-00594-v2.pdf ad5762937509c1e7cce4f96f0c6cb81dd66c2e8d4f22b67bd56ad3d82a7d0686 vaccines-13-00594-v2.pdf Title: Target Trial Emulation of the Modified Vaccinia Ankara-Bavarian Nordic Vaccine for Pre-Exposure Mpox Prevention in At-Risk Populations Subject: Background: The MVA-BN vaccine is considered effective for preventing mpox in key populations, based on observational studies, though no randomized trials have yet confirmed its effectiveness. Observational studies published to date rely on retrospective analyses of routine data, often missing information on relevant risk factors for mpox. Methods: Multi-country target trial emulation study with prospective data collection. Between 1 September 2022 and 15 June 2023, we recruited individuals eligible for mpox vaccination based on clinical history and exposure behaviors via healthcare centers and social venues in Spain, Peru, Panama, and Chile. Vaccinated individuals were paired with unvaccinated counterparts matched by mpox risk factors, country, recruitment date, and age. Follow-up continued via periodic surveys until 31 March 2024. The primary endpoint was symptomatic mpox occurrence 14 days post-vaccination. Results: The primary analysis included 1028 individuals (514 vaccinated, 514 unvaccinated) with a median follow-up time of 9.3 months (IQR 4.7–13.7). Mpox occurred in eight participants (0.8%): three vaccinated and five unvaccinated (HR 0.6; 95% CI 0.21–1.70). Adverse reactions were reported by 731 (49.6%) participants, predominantly skin reactions (703/1475; 47.7%), while systemic reactions occurred in 107 (7.3%). Long-lasting erythema at the injection site was reported in 450/1058 (42.5%) participants, persisting >6 months in 107 of them (23.8%). Conclusions: The low incidence of mpox during the study period resulted in a limited number of endpoint events, precluding robust conclusions on the efficacy of the MVA-BN vaccine as pre-exposure prevention for mpox. However, our analysis, which accounted for key confounders such as exposure behaviors, yielded results consistent with previous studies suggesting the effectiveness of the vaccine in the mpox setting. Keywords: mpox; vaccine; MVA-BN; efficacy; safety; target trial emulation Author: Clara Suñer, Roser Escrig-Sarreta, Cristina Galván-Casas, Eduardo Matos, Amanda Gabster, Marcelo Wolff, Dan Ouchi, Andrea Alemany, Hugo Sánchez, Sandra Huaman, Dixennia Bejarano, Lourdes Carrés-Esteve, Cristina Santiago-Fernández, Javier Corral-Rubio, Adrià Mendoza, Àngel Rivero, Vicente Descalzo, Eva Orviz, Héctor Martínez-Riveros, Leonardo Méndez-Boo, Carmen Cabezas, Araceli Arce-Arnáez, Michael Marks, Oriol Mitjà and REMAIN Study Group Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Wed Jun 4 07:36:28 2025 CEST ModDate: Wed Jun 4 08:01:33 2025 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 844906 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- ODASUJ+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 YOEXCO+VnURWPalladioL Type 1 Custom yes yes yes 16 0 WXYDIE+URWPalladioL-Roma Type 1 Custom yes yes yes 21 0 SIYABV+URWPalladioL-Bold Type 1 Custom yes yes yes 27 0 QJNQGP+URWPalladioL-Ital Type 1 Custom yes yes yes 32 0 PHPDYL+CMSY10 Type 1 Builtin yes yes yes 58 0 URYLRZ+URWPalladioL-BoldItal Type 1 Custom yes yes yes 75 0 KMIBFF+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 85 0 KMIBFH+PalatinoLinotype TrueType WinAnsi yes yes no 88 0 CIDFont+F1 CID TrueType Identity-H yes no yes 108 0 CIDFont+F2 CID TrueType Identity-H yes no yes 116 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-09-18 03:08:46 CEST RepresentationInformation: vaccines-13-00594-v2.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-09-17 12:03:55 CEST Size: 844906 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 260 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Study Design and Outcomes Destination: subsection.2.1 Item: Title: Participants and Matching for Trial Emulation Destination: subsection.2.2 Item: Title: Study Procedures and Definitions Destination: subsection.2.3 Item: Title: Sample Size and Statistical Methods Destination: subsection.2.4 Item: Title: Results Destination: section.3 Children: Item: Title: Study Participants and Follow-Up Destination: subsection.3.1 Item: Title: Vaccine Efficacy Destination: subsection.3.2 Item: Title: Vaccine Safety Destination: subsection.3.3 Item: Title: Discussion Destination: section.4 Item: Title: References Destination: appendix.A. Info: Title: Target Trial Emulation of the Modified Vaccinia Ankara-Bavarian Nordic Vaccine for Pre-Exposure Mpox Prevention in At-Risk Populations Author: Clara Suñer, Roser Escrig-Sarreta, Cristina Galván-Casas, Eduardo Matos, Amanda Gabster, Marcelo Wolff, Dan Ouchi, Andrea Alemany, Hugo Sánchez, Sandra Huaman, Dixennia Bejarano, Lourdes Carrés-Esteve, Cristina Santiago-Fernández, Javier Corral-Rubio, Adrià Mendoza, Àngel Rivero, Vicente Descalzo, Eva Orviz, Héctor Martínez-Riveros, Leonardo Méndez-Boo, Carmen Cabezas, Araceli Arce-Arnáez, Michael Marks, Oriol Mitjà and REMAIN Study Group Subject: Background: The MVA-BN vaccine is considered effective for preventing mpox in key populations, based on observational studies, though no randomized trials have yet confirmed its effectiveness. Observational studies published to date rely on retrospective analyses of routine data, often missing information on relevant risk factors for mpox. Methods: Multi-country target trial emulation study with prospective data collection. Between 1 September 2022 and 15 June 2023, we recruited individuals eligible for mpox vaccination based on clinical history and exposure behaviors via healthcare centers and social venues in Spain, Peru, Panama, and Chile. Vaccinated individuals were paired with unvaccinated counterparts matched by mpox risk factors, country, recruitment date, and age. Follow-up continued via periodic surveys until 31 March 2024. The primary endpoint was symptomatic mpox occurrence 14 days post-vaccination. Results: The primary analysis included 1028 individuals (514 vaccinated, 514 unvaccinated) with a median follow-up time of 9.3 months (IQR 4.7 13.7). Mpox occurred in eight participants (0.8%): three vaccinated and five unvaccinated (HR 0.6; 95% CI 0.21 1.70). Adverse reactions were reported by 731 (49.6%) participants, predominantly skin reactions (703/1475; 47.7%), while systemic reactions occurred in 107 (7.3%). Long-lasting erythema at the injection site was reported in 450/1058 (42.5%) participants, persisting >6 months in 107 of them (23.8%). Conclusions: The low incidence of mpox during the study period resulted in a limited number of endpoint events, precluding robust conclusions on the efficacy of the MVA-BN vaccine as pre-exposure prevention for mpox. However, our analysis, which accounted for key confounders such as exposure behaviors, yielded results consistent with previous studies suggesting the effectiveness of the vaccine in the mpox setting. 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