{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T07:39:48Z","timestamp":1794037188488,"version":"4.8.0"},"reference-count":41,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T00:00:00Z","timestamp":1692835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Prevention of mpox has become an important public health interest. We aimed to evaluate the safety and immunogenicity of the Modified Vaccinia Ankara (MVA) vaccine. We conducted a systematic review and meta-analysis of randomized-controlled trials (RCTs) comparing MVA versus no intervention, placebo, or another vaccine. Outcomes included safety and immunogenicity outcomes. We also performed a systematic review of RCTs evaluating various MVA regimens. Fifteen publications were included in the quantitative meta-analysis. All but one (ACAM2000) compared MVA with placebo. We found that cardiovascular adverse events following two MVA doses were significantly more common compared to placebo (relative risk [RR] 4.07, 95% confidence interval [CI] 1.10\u201315.10), though serious adverse events (SAEs) were not significantly different. Following a single MVA dose, no difference was demonstrated in any adverse event outcomes. Seroconversion rates were significantly higher compared with placebo after a single or two doses. None of the RCTs evaluated clinical effectiveness in preventing mpox. This meta-analysis provides reassuring results concerning the immunogenicity and safety of MVA. Further studies are needed to confirm the immunogenicity of a single dose and its clinical effectiveness. A single vaccine dose may be considered according to vaccine availability, with preference for two doses.<\/jats:p>","DOI":"10.3390\/vaccines11091410","type":"journal-article","created":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T10:06:48Z","timestamp":1692871608000},"page":"1410","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Immunogenicity and Safety of Modified Vaccinia Ankara (MVA) Vaccine\u2014A Systematic Review and Meta-Analysis of Randomized Controlled Trials"],"prefix":"10.3390","volume":"11","author":[{"given":"Lior","family":"Nave","sequence":"first","affiliation":[{"name":"Internal Medicine E, Sheba Medical Center, Ramat-Gan 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2622-418X","authenticated-orcid":false,"given":"Ili","family":"Margalit","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Tel Aviv University, Ramat-Aviv, Tel Aviv 69978, Israel"},{"name":"Infectious Diseases Unit, Sheba Medical Center, Ramat-Gan 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0849-1708","authenticated-orcid":false,"given":"Noam","family":"Tau","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Tel Aviv University, Ramat-Aviv, Tel Aviv 69978, Israel"},{"name":"Department of Diagnostic Imaging, Sheba Medical Center, Ramat-Gan 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ido","family":"Cohen","sequence":"additional","affiliation":[{"name":"Internal Medicine E, Sheba Medical Center, Ramat-Gan 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Yelin","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Tel Aviv University, Ramat-Aviv, Tel Aviv 69978, Israel"},{"name":"Infectious Diseases Unit, Sheba Medical Center, Ramat-Gan 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9161-7107","authenticated-orcid":false,"given":"Florian","family":"Lienert","sequence":"additional","affiliation":[{"name":"Bavarian Nordic AG, CH-6301 Zug, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3181-9791","authenticated-orcid":false,"given":"Dafna","family":"Yahav","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Tel Aviv University, Ramat-Aviv, Tel Aviv 69978, Israel"},{"name":"Infectious Diseases Unit, Sheba Medical Center, Ramat-Gan 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,24]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (WHO) (2022). Disease Outbreak News; Multi-Country Mpox Outbreak in Non-Endemic Countries, World Health Organization. Available online: https:\/\/www.who.int\/emergencies\/disease-outbreak-news\/item\/2022-DON385."},{"key":"ref_2","first-page":"123","article-title":"Newer Poxvirus Vaccine Is Recommended","volume":"328","author":"Kuehn","year":"2022","journal-title":"JAMA"},{"key":"ref_3","first-page":"1","article-title":"Smallpox vaccination and adverse reactions. Guidance for clinicians","volume":"52","author":"Cono","year":"2003","journal-title":"MMWR Recomm. Rep. Morb. Mortal. Wkly. Rep. Recomm. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2734","DOI":"10.1001\/jama.294.21.2734","article-title":"Adverse events associated with smallpox vaccination in the United States, January\u2013October 2003","volume":"294","author":"Casey","year":"2005","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.3389\/fimmu.2018.01963","article-title":"New Vaccine Technologies to Combat Outbreak Situations","volume":"9","author":"Rauch","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/BF01641272","article-title":"Abstammung, Eigenschaften und Verwendung des attenuierten Vaccinia-Stammes MVA","volume":"3","author":"Mayr","year":"1975","journal-title":"Infection"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.1016\/j.vaccine.2012.02.016","article-title":"Biosafety aspects of modified vaccinia virus Ankara (MVA)-based vectors used for gene therapy or vaccination","volume":"30","author":"Verheust","year":"2012","journal-title":"Vaccine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7442","DOI":"10.1016\/j.vaccine.2009.05.095","article-title":"Modified vaccinia Ankara strains with identical coding sequences actually represent complex mixtures of viruses that determine the biological properties of each strain","volume":"27","author":"Suter","year":"2009","journal-title":"Vaccine"},{"key":"ref_9","unstructured":"CDC (Centers for Disease Control and Prevention) (2023, July 15). Risk of Resurgent Mpox Outbreaks Warrants Increased Prevention Effort, Available online: https:\/\/www.cdc.gov\/poxvirus\/mpox\/cases-data\/risk-assessment\/may-2023.html."},{"key":"ref_10","unstructured":"World Health Organization (WHO) (2022). Vaccines and Immunization for Monkeypox, World Health Organization. Available online: WHO-MPX-Immunization-2022.2-eng.pdf."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_12","unstructured":"Higgins, J.P.T. (2023, July 15). Cochrane Handbook for Systematic Reviews of Interventions. Available online: www.handbook.cochrane.org."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5425","DOI":"10.1016\/j.vaccine.2015.08.032","article-title":"Sex difference in immune response to vaccination: A participant-level meta-analysis of randomized trials of IMVAMUNE smallpox vaccine","volume":"33","author":"Troy","year":"2015","journal-title":"Vaccine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1056\/NEJMoa1817307","article-title":"Phase 3 Efficacy Trial of Modified Vaccinia Ankara as a Vaccine against Smallpox","volume":"381","author":"Pittman","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Greenberg, R.N., Hay, C.M., Stapleton, J.T., Marbury, T.C., Wagner, E., Kreitmeir, E., R\u00f6esch, S., von Krempelhuber, A., Young, P., and Nichols, R. (2016). A Randomized, Double-Blind, Placebo-Controlled Phase II Trial Investigating the Safety and Immunogenicity of Modified Vaccinia Ankara Smallpox Vaccine (MVA-BN\u00ae) in 56-80-Year-Old Subjects. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157335"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/j.vaccine.2006.10.047","article-title":"Safety, immunogenicity and efficacy of modified vaccinia Ankara (MVA) against Dryvax challenge in vaccinia-na\u00efve and vaccinia-immune individuals","volume":"25","author":"Parrino","year":"2007","journal-title":"Vaccine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1093\/infdis\/jit105","article-title":"Safety and immunogenicity of modified vaccinia Ankara in hematopoietic stem cell transplant recipients: A randomized, controlled trial","volume":"207","author":"Walsh","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2600","DOI":"10.1016\/j.vaccine.2020.01.058","article-title":"A randomized phase II trial to compare safety and immunogenicity of the MVA-BN smallpox vaccine at various doses in adults with a history of AIDS","volume":"38","author":"Overton","year":"2020","journal-title":"Vaccine"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zitzmann-Roth, E.M., von Sonnenburg, F., de la Motte, S., Arndtz-Wiedemann, N., von Krempelhuber, A., Uebler, N., Vollmar, J., Virgin, G., and Chaplin, P. (2015). Cardiac safety of Modified Vaccinia Ankara for vaccination against smallpox in a young, healthy study population. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0122653"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8562","DOI":"10.1016\/j.vaccine.2007.10.017","article-title":"Clinical and immunologic responses to multiple doses of IMVAMUNE (Modified Vaccinia Ankara) followed by Dryvax challenge","volume":"25","author":"Frey","year":"2007","journal-title":"Vaccine"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Overton, E.T., Lawrence, S.J., Wagner, E., Nopora, K., R\u00f6sch, S., Young, P., Schmidt, D., Kreusel, C., De Carli, S., and Meyer, T.P. (2018). Immunogenicity and safety of three consecutive production lots of the non replicating smallpox vaccine MVA: A randomised, double blind, placebo controlled phase III trial. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0195897"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1093\/infdis\/jiac455","article-title":"One- and Two-Dose Vaccinations with Modified Vaccinia Ankara-Bavarian Nordic Induce Durable B-Cell Memory Responses Comparable to Replicating Smallpox Vaccines","volume":"227","author":"Ilchmann","year":"2023","journal-title":"J. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2732","DOI":"10.1016\/j.vaccine.2014.02.043","article-title":"Phase II randomized, double-blinded comparison of a single high dose (5 \u00d7 108 TCID50) of modified vaccinia Ankara compared to a standard dose (1 \u00d7 108 TCID50) in healthy vaccinia-na\u00efve individuals","volume":"32","author":"Frey","year":"2014","journal-title":"Vaccine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5225","DOI":"10.1016\/j.vaccine.2015.06.075","article-title":"Comparison of lyophilized versus liquid modified vaccinia Ankara (MVA) formulations and subcutaneous versus intradermal routes of administration in healthy vaccinia-na\u00efve subjects","volume":"33","author":"Frey","year":"2015","journal-title":"Vaccine"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/j.vaccine.2009.11.030","article-title":"A randomized, double-blind, dose-finding Phase II study to evaluate immunogenicity and safety of the third generation smallpox vaccine candidate IMVAMUNE","volume":"28","author":"Vollmar","year":"2010","journal-title":"Vaccine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1016\/j.vaccine.2005.11.022","article-title":"Safety and immunogenicity of IMVAMUNE, a promising candidate as a third generation smallpox vaccine","volume":"24","author":"Vollmar","year":"2006","journal-title":"Vaccine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1016\/j.vaccine.2017.02.032","article-title":"Safety and immunogenicity of a modified vaccinia Ankara vaccine using three immunization schedules and two modes of delivery: A randomized clinical non-inferiority trial","volume":"35","author":"Jackson","year":"2017","journal-title":"Vaccine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.vaccine.2022.10.056","article-title":"A randomized phase 3 trial to assess the immunogenicity and safety of 3 consecutively produced lots of freeze-dried MVA-BN\u00ae vaccine in healthy adults","volume":"41","author":"Overton","year":"2023","journal-title":"Vaccine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1016\/j.vaccine.2013.04.050","article-title":"Safety and immunogenicity of IMVAMUNE\u00ae smallpox vaccine using different strategies for a post event scenario","volume":"31","author":"Frey","year":"2013","journal-title":"Vaccine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"734","DOI":"10.15585\/mmwr.mm7122e1","article-title":"Use of JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) for Preexposure Vaccination of Persons at Risk for Occupational Exposure to Orthopoxviruses: Recommendations of the Advisory Committee on Immunization Practices\u2014United States, 2022","volume":"71","author":"Rao","year":"2022","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2434","DOI":"10.1056\/NEJMoa2215201","article-title":"Vaccine Effectiveness of JYNNEOS against Mpox Disease in the United States","volume":"388","author":"Deputy","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"553","DOI":"10.15585\/mmwr.mm7220a3","article-title":"Estimated Effectiveness of JYNNEOS Vaccine in Preventing Mpox: A Multijurisdictional Case-Control Study\u2014United States, 19 August 2022\u201331 March 2023","volume":"72","author":"Dalton","year":"2023","journal-title":"Morb. Mortal. Wkly. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"559","DOI":"10.15585\/mmwr.mm7220a4","article-title":"Effectiveness of JYNNEOS Vaccine against Diagnosed Mpox Infection\u2014New York, 2022","volume":"72","author":"Rosenberg","year":"2023","journal-title":"Morb. Mortal. Wkly. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.15585\/mmwr.mm7149a5","article-title":"Reduced Risk for Mpox after Receipt of 1 or 2 Doses of JYNNEOS Vaccine Compared with Risk among Unvaccinated Persons\u201443 U.S. Jurisdictions, 31 July\u20131 October 2022","volume":"71","author":"Payne","year":"2022","journal-title":"Morb. Mortal. Wkly. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1038\/s41591-023-02229-3","article-title":"Real-world effectiveness of a single dose of mpox vaccine in males","volume":"29","author":"Sagy","year":"2023","journal-title":"Nat. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/S1473-3099(23)00057-9","article-title":"Effectiveness of one dose of MVA-BN smallpox vaccine against mpox in England using the case-coverage method: An observational study","volume":"23","author":"Bertran","year":"2023","journal-title":"Lancet Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Malone, S.M., Mitra, A.K., Onumah, N.A., Brown, A., Jones, L.M., Tresvant, D., Brown, C.S., Onyia, A.U., and Iseguede, F.O. (2023). Safety and Efficacy of Post-Eradication Smallpox Vaccine as an Mpox Vaccine: A Systematic Review with Meta-Analysis. Int. J. Environ. Res. Public Health, 20.","DOI":"10.3390\/ijerph20042963"},{"key":"ref_38","unstructured":"Food and Drug Administration (FDA) (2023, July 15). JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) Suspension for Subcutaneous Injection Initial U.S. Approval: 2019, Available online: https:\/\/www.fda.gov\/media\/131078\/download."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1056\/NEJMra2208860","article-title":"Monkeypox","volume":"387","author":"Gessain","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1093\/infdis\/jis753","article-title":"Safety, immunogenicity, and surrogate markers of clinical efficacy for modified vaccinia Ankara as a smallpox vaccine in HIV-infected subjects","volume":"207","author":"Greenberg","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"ofv040","DOI":"10.1093\/ofid\/ofv040","article-title":"Safety and Immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine in Vaccinia-Naive and Experienced Human Immunodeficiency Virus-Infected Individuals: An Open-Label, Controlled Clinical Phase II Trial","volume":"Volume 2","author":"Overton","year":"2015","journal-title":"Open Forum Infectious Diseases"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/11\/9\/1410\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:38:08Z","timestamp":1760128688000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/11\/9\/1410"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,24]]},"references-count":41,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["vaccines11091410"],"URL":"https:\/\/doi.org\/10.3390\/vaccines11091410","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,24]]}}}