{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:12:58Z","timestamp":1787962378364,"version":"build-2784847793"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T00:00:00Z","timestamp":1668124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Serum Institute of India Pvt Ltd"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Bacille Calmette-Gu\u00e9rin (BCG) vaccination can potentially reduce the rate of respiratory infections in vulnerable populations. This study evaluates the safety and efficacy of VPM1002 (a genetically modified BCG) as prophylaxis against severe respiratory tract infections including coronavirus disease 2019 (COVID-19) in an elderly population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this phase 3, randomized, double-blind, placebo-controlled, multicenter clinical trial, healthy elderly volunteers (N = 2064) were enrolled, randomized (1:1) to receive either VPM1002 or placebo, and followed up remotely for 240 days. The primary outcome was the mean number of days with severe respiratory infections at hospital and\/or at home. Secondary endpoints included the incidence of self-reported fever, number of hospital and intensive care unit (ICU) admissions, and number of adverse events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 31 participants in the VPM1002 group reported at least 1 day with severe respiratory disease and a mean number of days with severe respiratory disease of 9.39 \u00b1 9.28 while in the placebo group; 38 participants reported a mean of 14.29 \u00b1 16.25 days with severe respiratory disease. The incidence of self-reported fever was lower in the VPM1002 group (odds ratio, 0.46 [95% confidence interval, .28\u2013.74]; P = .001), and consistent trends to fewer hospitalization and ICU admissions due to COVID-19 were observed after VPM1002 vaccination. Local reactions typical for BCG were observed in the VPM1002-vaccinated group, which were mostly of mild intensity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Vaccination with VPM1002 is well tolerated and seems to have a prophylactic effect against severe respiratory disease in the elderly.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trials Registration<\/jats:title><jats:p>NCT04435379.<\/jats:p><\/jats:sec>","DOI":"10.1093\/cid\/ciac881","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T23:07:53Z","timestamp":1668035273000},"page":"1304-1310","source":"Crossref","is-referenced-by-count":33,"title":["VPM1002 as Prophylaxis Against Severe Respiratory Tract Infections Including Coronavirus Disease 2019 in the Elderly: A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Study"],"prefix":"10.1093","volume":"76","author":[{"given":"Alexandra M","family":"Blossey","sequence":"first","affiliation":[{"name":"Vakzine Projekt Management GmbH , Hannover , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sina","family":"Br\u00fcckner","sequence":"additional","affiliation":[{"name":"Vakzine Projekt Management GmbH , Hannover , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"May","sequence":"additional","affiliation":[{"name":"Vakzine Projekt Management GmbH , Hannover , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald P","family":"Parzmair","sequence":"additional","affiliation":[{"name":"Vakzine Projekt Management GmbH , Hannover , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitt","family":"Sharma","sequence":"additional","affiliation":[{"name":"Serum Institute of India Private Limited , Pune , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umesh","family":"Shaligram","sequence":"additional","affiliation":[{"name":"Serum Institute of India Private Limited , Pune , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leander","family":"Grode","sequence":"additional","affiliation":[{"name":"Vakzine Projekt Management GmbH , Hannover , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan H E","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Infection Biology , Berlin , Germany"},{"name":"Hagler Institute for Advanced Study, Texas A&M University , College Station, Texas , USA"},{"name":"Max Planck Institute for Multidisciplinary Sciences , G\u00f6ttingen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai G","family":"Netea","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center , Nijmegen , The Netherlands"},{"name":"Radboud Center for Infectious Diseases, Radboud University Medical Center , Nijmegen , The Netherlands"},{"name":"Department for Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn , Bonn , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Schindler","sequence":"additional","affiliation":[{"name":"Clinical Research Center Core Facility, Hannover Medical School , Hannover , Germany"},{"name":"Center for Pharmacology and Toxicology, Hannover Medical School , Hannover , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,11,11]]},"reference":[{"key":"2023040319412878700_","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.maturitas.2015.05.004","article-title":"Immunosenescence: implications for response to infection and vaccination in older people","volume":"82","author":"Pera","year":"2015","journal-title":"Maturitas"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/s41586-020-2521-4","article-title":"Factors associated with COVID-19-related death using OpenSAFELY","volume":"584","author":"Williamson","year":"2020","journal-title":"Nature"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/s41577-020-0337-y","article-title":"BCG-induced trained immunity: can it offer protection against COVID-19?","volume":"20","author":"O\u2019Neill","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"2023040319412878700_","first-page":"1481","article-title":"Preventive vaccination against tuberculosis with BCG","volume":"24","author":"Calmette","year":"1931","journal-title":"Proc R Soc Med"},{"key":"2023040319412878700_","first-page":"233","article-title":"WHO report 2007: global tuberculosis control\u2014surveillance, planning, financing","volume":"126","author":"Behera","year":"2007","journal-title":"Indian J Med Res"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","first-page":"e2","DOI":"10.1016\/S1473-3099(21)00403-5","article-title":"100 Years of Mycobacterium bovis bacille Calmette-Guerin","volume":"22","author":"Lange","year":"2022","journal-title":"Lancet Infect Dis"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1016\/j.cmi.2019.04.020","article-title":"Non-specific effects of BCG vaccine on viral infections","volume":"25","author":"Moorlag","year":"2019","journal-title":"Clin Microbiol Infect"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1038\/s41467-019-08659-3","article-title":"Outcomes of controlled human malaria infection after BCG vaccination","volume":"10","author":"Walk","year":"2019","journal-title":"Nat Commun"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.cell.2020.08.051","article-title":"Activate: randomized clinical trial of BCG vaccination against infection in the elderly","volume":"183","author":"Giamarellos-Bourboulis","year":"2020","journal-title":"Cell"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/s41541-018-0062-8","article-title":"Long-term reduction in hyperglycemia in advanced type 1 diabetes: the value of induced aerobic glycolysis with BCG vaccinations","volume":"3","author":"Kuhtreiber","year":"2018","journal-title":"NPJ Vaccines"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/S0022-5347(17)58737-6","article-title":"Intracavitary bacillus Calmette-Guerin in the treatment of superficial bladder tumors","volume":"116","author":"Morales","year":"1976","journal-title":"J Urol"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1200\/JCO.1995.13.6.1404","article-title":"Intravesical bacillus Calmette-Guerin therapy prevents tumor progression and death from superficial bladder cancer: ten-year follow-up of a prospective randomized trial","volume":"13","author":"Herr","year":"1995","journal-title":"J Clin Oncol"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/S0140-6736(20)31025-4","article-title":"Considering BCG vaccination to reduce the impact of COVID-19","volume":"395","author":"Curtis","year":"2020","journal-title":"Lancet"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.cell.2020.04.042","article-title":"Trained immunity: a tool for reducing susceptibility to and the severity of SARS-CoV-2 infection","volume":"181","author":"Netea","year":"2020","journal-title":"Cell"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2025448119","article-title":"Heterologous vaccination interventions to reduce pandemic morbidity and mortality: modeling the US winter 2020 COVID-19 wave","volume":"119:","author":"Hupert","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.1172\/JCI24617","article-title":"Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guerin mutants that secrete listeriolysin","volume":"115","author":"Grode","year":"2005","journal-title":"J Clin Invest"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1016\/j.vaccine.2012.12.053","article-title":"Safety and immunogenicity of the recombinant BCG vaccine VPM1002 in a phase 1 open-label randomized clinical trial","volume":"31","author":"Grode","year":"2013","journal-title":"Vaccine"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","DOI":"10.1128\/CVI.00439-16","article-title":"Safety and immunogenicity of the recombinant Mycobacterium bovis BCG vaccine VPM1002 in HIV-unexposed newborn infants in South Africa","volume":"24:","author":"Loxton","year":"2017","journal-title":"Clin Vaccine Immunol"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1016\/S1473-3099(22)00222-5","article-title":"Safety and immunogenicity of VPM1002 versus BCG in South African newborn babies: a randomised, phase 2 non-inferiority double-blind controlled trial","volume":"22","author":"Cotton","year":"2022","journal-title":"Lancet Infect Dis"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","first-page":"316","DOI":"10.3389\/fimmu.2020.00316","article-title":"Vaccination against tuberculosis: revamping BCG by molecular genetics guided by immunology","volume":"11:","author":"Kaufmann","year":"2020","journal-title":"Front Immunol"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","first-page":"e938","DOI":"10.1093\/cid\/ciac182","article-title":"Efficacy of BCG vaccination against respiratory tract infections in older adults during the coronavirus disease 2019 pandemic","volume":"75","author":"Moorlag","year":"2022","journal-title":"Clin Infect Dis"},{"key":"2023040319412878700_","author":"World Health Organization"},{"key":"2023040319412878700_","author":"National Cancer Institute","year":"2006"},{"key":"2023040319412878700_","author":"Centers for Disease Control and Prevention"},{"key":"2023040319412878700_","first-page":"185","article-title":"The efficacy of Bacillus Calmette-Guerin vaccinations for the prevention of acute upper respiratory tract infection in the elderly","volume":"43","author":"Wardhana","year":"2011","journal-title":"Acta Med Indones"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","first-page":"34","DOI":"10.3143\/geriatrics.42.34","article-title":"Prevention of elderly pneumonia by pneumococcal, influenza and BCG vaccinations [in Japanese]","volume":"42","author":"Ohrui","year":"2005","journal-title":"Nihon Ronen Igakkai Zasshi"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","first-page":"841868","DOI":"10.3389\/fimmu.2022.841868","article-title":"Efficacy and safety of BCG revaccination with M. bovis BCG Moscow to prevent COVID-19 infection in health care workers: a randomized phase II clinical trial","volume":"13","author":"Anjos LRB","year":"2022","journal-title":"Front Immunol"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20211862","article-title":"Intravenous administration of BCG protects mice against lethal SARS-CoV-2 challenge","volume":"219","author":"Hilligan","year":"2022","journal-title":"J Exp Med"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","first-page":"314","DOI":"10.3390\/vaccines10020314","article-title":"A multi-center, randomised, double-blind, placebo-controlled phase III clinical trial evaluating the impact of BCG re-vaccination on the incidence and severity of SARS-CoV-2 infections among symptomatic healthcare professionals during the COVID-19 pandemic in Poland\u2014first results","volume":"10","author":"Czajka","year":"2022","journal-title":"Vaccines"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","first-page":"110502","DOI":"10.1016\/j.celrep.2022.110502","article-title":"BCG vaccination provides protection against IAV but not SARS-CoV-2","volume":"38","author":"Kaufmann","year":"2022","journal-title":"Cell Rep"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","first-page":"101414","DOI":"10.1016\/j.eclinm.2022.101414","article-title":"Safety and efficacy of BCG re-vaccination in relation to COVID-19 morbidity in healthcare workers: a double-blind, randomised, controlled, phase 3 trial","volume":"48","author":"Upton","year":"2022","journal-title":"EClinicalMedicine"},{"key":"2023040319412878700_","article-title":"BCG revaccination qualitatively and quantitatively enhances SARS-CoV-2 spike-specific neutralizing antibody and T cell responses induced by the COVISHIELDTM vaccine in SARS-CoV-2 seronegative young Indian adults","author":"Rakshit","year":"2022","journal-title":"Res Sq"},{"key":"2023040319412878700_","doi-asserted-by":"crossref","first-page":"3179","DOI":"10.3390\/cells10113179","article-title":"Effect of BCG revaccination on occupationally exposed medical personnel vaccinated against SARS-CoV-2","volume":"10:","author":"Ramos-Martinez","year":"2021","journal-title":"Cells"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciac881\/47646184\/ciac881.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/76\/7\/1304\/49734364\/ciac881.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/76\/7\/1304\/49734364\/ciac881.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T15:03:15Z","timestamp":1701356595000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/76\/7\/1304\/6821343"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,11]]},"references-count":33,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,11,11]]},"published-print":{"date-parts":[[2023,4,3]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciac881","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,4,1]]},"published":{"date-parts":[[2022,11,11]]}}}