{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T09:28:10Z","timestamp":1768296490006,"version":"3.49.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T00:00:00Z","timestamp":1598572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>WHO convened an Advisory Group (AG) to consider the feasibility, potential value, and limitations of establishing a closely-monitored challenge model of experimental severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) in healthy adult volunteers. The AG included experts in design, establishment, and performance of challenges. This report summarizes issues that render a COVID-19 model daunting to establish (the potential of SARS-CoV-2 to cause severe\/fatal illness, its high transmissibility, and lack of a \u201crescue treatment\u201d to prevent progression from mild\/moderate to severe clinical illness) and it proffers prudent strategies for stepwise model development, challenge virus selection, guidelines for manufacturing challenge doses, and ways to contain SARS-CoV-2 and prevent transmission to household\/community contacts. A COVID-19 model could demonstrate protection against virus shedding and\/or illness induced by prior SARS-CoV-2 challenge or vaccination. A limitation of the model is that vaccine efficacy in experimentally challenged healthy young adults cannot per se be extrapolated to predict efficacy in elderly\/high-risk adults.<\/jats:p>","DOI":"10.1093\/cid\/ciaa1290","type":"journal-article","created":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T19:13:35Z","timestamp":1598469215000},"page":"2035-2041","source":"Crossref","is-referenced-by-count":16,"title":["Viewpoint of a WHO Advisory Group Tasked to Consider Establishing a Closely-monitored Challenge Model of Coronavirus Disease 2019 (COVID-19) in Healthy Volunteers"],"prefix":"10.1093","volume":"72","author":[{"given":"Myron M","family":"Levine","sequence":"first","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salim","family":"Abdullah","sequence":"additional","affiliation":[{"name":"Ifakara Health Institute (IHI), Ifakara, Tanzania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaseen M","family":"Arabi","sequence":"additional","affiliation":[{"name":"College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Kingdom of Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Delese Mimi","family":"Darko","sequence":"additional","affiliation":[{"name":"CEO, FDA, Cantonments, Accra, Ghana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna P","family":"Durbin","sequence":"additional","affiliation":[{"name":"Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vicente","family":"Estrada","sequence":"additional","affiliation":[{"name":"Medical School, Complutense University, Hospital Cl\u00ednico San Carlos, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Euzebiusz","family":"Jamrozik","sequence":"additional","affiliation":[{"name":"Monash Bioethics Centre, Monash University, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter G","family":"Kremsner","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Tropenmedizin, Universit\u00e4tsklinikum T\u00fcbingen, Germany"},{"name":"Centre de Recherches M\u00e9dicales de Lambar\u00e9n\u00e9, Gabon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosanna","family":"Lagos","sequence":"additional","affiliation":[{"name":"Centro para Vacunas en Desarrollo (CVD-Chile), Santiago, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Punnee","family":"Pitisuttithum","sequence":"additional","affiliation":[{"name":"Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanley A","family":"Plotkin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pennsylvania, Doylestown, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Sauerwein","sequence":"additional","affiliation":[{"name":"Medical Parasitology Department, Radboud University, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng-Li","family":"Shi","sequence":"additional","affiliation":[{"name":"Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Halvor","family":"Sommerfelt","sequence":"additional","affiliation":[{"name":"Centre for Intervention Science in Maternal and Child Health, Department of Global Public Health and Primary Care, University of Bergen, Bergen, and Norwegian Institute of Public Health, Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanta","family":"Subbarao","sequence":"additional","affiliation":[{"name":"WHO Collaborating Centre for Reference and Research on Influenza and Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute, Melbourne, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John J","family":"Treanor","sequence":"additional","affiliation":[{"name":"Infectious Diseases Division, University of Rochester Medical Center, Rochester, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sudhanshu","family":"Vrati","sequence":"additional","affiliation":[{"name":"Regional Centre for Biotechnology, Haryana (NCR Delhi), India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"King","sequence":"additional","affiliation":[{"name":"Vaccines Priority Area, Wellcome Trust, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shobana","family":"Balasingam","sequence":"additional","affiliation":[{"name":"Vaccines, Wellcome Trust, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlie","family":"Weller","sequence":"additional","affiliation":[{"name":"Vaccines Programme, Wellcome Trust, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastazia Older","family":"Aguilar","sequence":"additional","affiliation":[{"name":"Global Health Discovery & Translational Sciences, Bill & Melinda Gates Foundation, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M Cristina","family":"Cassetti","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip R","family":"Krause","sequence":"additional","affiliation":[{"name":"Office of Vaccines Research and Review, CEBR, FDA, Silver Spring, Maryland, USA"},{"name":"Chair, WHO R&D Blueprint COVID-19 Vaccines Working Group"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Maria Henao","family":"Restrepo","sequence":"additional","affiliation":[{"name":"Office of the Executive Director (WHE), WHO Health Emergencies Programme, World Health Organization, Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,8,28]]},"reference":[{"key":"2021060106125076800_CIT0001","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1126\/science.352.6288.882","article-title":"The Truest Test","volume":"352","author":"Cohen","year":"2016","journal-title":"Science"},{"key":"2021060106125076800_CIT0002","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1093\/cid\/ciw145","article-title":"Single-dose live oral cholera vaccine CVD 103-HgR protects against human experimental infection with vibrio cholerae O1 El Tor","volume":"62","author":"Chen","year":"2016","journal-title":"Clin Infect Dis"},{"key":"2021060106125076800_CIT0003","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1080\/14760584.2017.1291348","article-title":"PaxVax CVD 103-HgR single-dose live oral cholera vaccine","volume":"16","author":"Levine","year":"2017","journal-title":"Expert Rev Vaccines"},{"key":"2021060106125076800_CIT0004","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1056\/NEJM199701093360202","article-title":"A preliminary evaluation of a recombinant circumsporozoite protein vaccine against Plasmodium falciparum malaria. RTS,S Malaria Vaccine Evaluation Group","volume":"336","author":"Stoute","year":"1997","journal-title":"N Engl J Med"},{"key":"2021060106125076800_CIT0005","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.1073\/pnas.1615324114","article-title":"Attenuated PfSPZ Vaccine induces strain-transcending T cells and durable protection against heterologous controlled human malaria infection","volume":"114","author":"Lyke","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2021060106125076800_CIT0006","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/S0264-410X(99)00334-5","article-title":"Evaluation of trivalent, live, cold-adapted (CAIV-T) and inactivated (TIV) influenza vaccines in prevention of virus infection and illness following challenge of adults with wild-type influenza A (H1N1), A (H3N2), and B viruses","volume":"18","author":"Treanor","year":"1999","journal-title":"Vaccine"},{"key":"2021060106125076800_CIT0007","doi-asserted-by":"crossref","first-page":"7075","DOI":"10.1016\/j.vaccine.2015.09.052","article-title":"Dengue human infection models to advance dengue vaccine development","volume":"33","author":"Larsen","year":"2015","journal-title":"Vaccine"},{"key":"2021060106125076800_CIT0008","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.1016\/S0140-6736(17)32149-9","article-title":"Efficacy and immunogenicity of a Vi-tetanus toxoid conjugate vaccine in the prevention of typhoid fever using a controlled human infection model of Salmonella typhi: a randomised controlled, phase 2b trial","volume":"390","author":"Jin","year":"2017","journal-title":"Lancet"},{"key":"2021060106125076800_CIT0009","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1080\/21645515.2019.1578922","article-title":"A roadmap for enterotoxigenic Escherichia coli vaccine development based on volunteer challenge studies","volume":"15","author":"Levine","year":"2019","journal-title":"Hum Vaccin Immunother"},{"key":"2021060106125076800_CIT0010","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nri2902","article-title":"Experimental human challenge infections can accelerate clinical malaria vaccine development","volume":"11","author":"Sauerwein","year":"2011","journal-title":"Nat Rev Immunol"},{"key":"2021060106125076800_CIT0011","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1093\/infdis\/155.6.1260","article-title":"Prevention of shigellosis by a Salmonella typhi-Shigella sonnei bivalent vaccine","volume":"155","author":"Black","year":"1987","journal-title":"J Infect Dis"},{"key":"2021060106125076800_CIT0012","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.1056\/NEJMoa1101245","article-title":"Norovirus vaccine against experimental human Norwalk Virus illness","volume":"365","author":"Atmar","year":"2011","journal-title":"N Engl J Med"},{"key":"2021060106125076800_CIT0013","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1016\/S0264-410X(98)00327-2","article-title":"A live attenuated chimeric recombinant parainfluenza virus (PIV) encoding the internal proteins of PIV type 3 and the surface glycoproteins of PIV type 1 induces complete resistance to PIV1 challenge and partial resistance to PIV3 challenge","volume":"17","author":"Tao","year":"1999","journal-title":"Vaccine"},{"key":"2021060106125076800_CIT0014","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nature21060","article-title":"Sterile protection against human malaria by chemoattenuated PfSPZ vaccine","volume":"542","author":"Mordm\u00fcller","year":"2017","journal-title":"Nature"},{"key":"2021060106125076800_CIT0015","doi-asserted-by":"crossref","first-page":"338","DOI":"10.4269\/ajtmh.17-1014","article-title":"Safety, immunogenicity, and protective efficacy against controlled human malaria infection of Plasmodium falciparum sporozoite vaccine in Tanzanian adults","volume":"99","author":"Jongo","year":"2018","journal-title":"Am J Trop Med Hyg"},{"key":"2021060106125076800_CIT0016","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1093\/infdis\/jiaa152","article-title":"Human challenge studies to accelerate coronavirus vaccine licensure","volume":"221","author":"Eyal","year":"2020","journal-title":"J Infect Dis"},{"key":"2021060106125076800_CIT0017","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1126\/science.368.6486.16","article-title":"Infect volunteers to speed a coronavirus vaccine?","volume":"368","author":"Cohen","year":"2020","journal-title":"Science"},{"key":"2021060106125076800_CIT0018","doi-asserted-by":"crossref","first-page":"3987","DOI":"10.1016\/j.vaccine.2020.04.039","article-title":"Extraordinary diseases require extraordinary solutions","volume":"38","author":"Plotkin","year":"2020","journal-title":"Vaccine"},{"key":"2021060106125076800_CIT0019","article-title":"It is time to address airborne transmission of COVID-19","author":"Morawska","year":"2020","journal-title":"Clin Infect Dis"},{"key":"2021060106125076800_CIT0020","volume-title":"Key criteria for the ethical acceptability of COVID-19 human challenge studies","author":"WHO Working Group for Guidance on Human Challenge Studies in COVID-19","year":"2020"},{"key":"2021060106125076800_CIT0021","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S1473-3099(08)70304-9","article-title":"Framework for the design and operation of high-level isolation units: consensus of the European Network of Infectious Diseases","volume":"9","author":"Bannister","year":"2009","journal-title":"Lancet Infect Dis"},{"key":"2021060106125076800_CIT0022","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S1473-3099(09)70070-2","article-title":"Infection control in the management of highly pathogenic infectious diseases: consensus of the European Network of Infectious Disease","volume":"9","author":"Brouqui","year":"2009","journal-title":"Lancet Infect Dis"},{"key":"2021060106125076800_CIT0023","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1513\/AnnalsATS.201509-587PS","article-title":"The creation of a biocontainment unit at a tertiary care hospital. The Johns Hopkins Medicine Experience","volume":"13","author":"Garibaldi","year":"2016","journal-title":"Ann Am Thorac Soc"},{"key":"2021060106125076800_CIT0024","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1111\/j.1748-720X.2007.00185.x","article-title":"Through the quarantine looking glass: drug-resistant tuberculosis and public health governance, law, and ethics","volume":"35","author":"Fidler","year":"2007","journal-title":"J Law Med Ethics"},{"key":"2021060106125076800_CIT0025","doi-asserted-by":"crossref","first-page":"e28","DOI":"10.1056\/NEJMp2004211","article-title":"Covid-19 - The law and limits of quarantine","volume":"382","author":"Parmet","year":"2020","journal-title":"N Engl J Med"},{"key":"2021060106125076800_CIT0026","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/0035-9203(79)90120-2","article-title":"The problem of emesis during oral glucose-electrolytes therapy given from the onset of severe cholera","volume":"73","author":"Nalin","year":"1979","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"2021060106125076800_CIT0027","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.2217\/fmb-2019-0196","article-title":"Poliopolis: pushing boundaries of scientific innovations for disease eradication","volume":"14","author":"Van","year":"2019","journal-title":"Future Microbiol"},{"key":"2021060106125076800_CIT0028","volume-title":"Human challenge studies in endemic settings: ethical and regulatory issues. Springer briefs in ethics","author":"Jamrozik","year":"2020"},{"key":"2021060106125076800_CIT0029","doi-asserted-by":"crossref","first-page":"717","DOI":"10.3389\/fimmu.2020.00717","article-title":"Vaccines to prevent infectious diseases in the older population: immunological challenges and future perspectives","volume":"11","author":"Wagner","year":"2020","journal-title":"Front Immunol"},{"key":"2021060106125076800_CIT0030","article-title":"How are vaccines assessed in clinical trials?","author":"Levine","year":"2016","edition":"2"},{"key":"2021060106125076800_CIT0031","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/S0140-6736(15)61117-5","article-title":"Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial","volume":"386","author":"Henao-Restrepo","year":"2015","journal-title":"Lancet"},{"key":"2021060106125076800_CIT0032","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1056\/NEJMoa1502924","article-title":"Phase 1 trials of rVSV Ebola vaccine in Africa and Europe\u2014preliminary report","volume":"374","author":"Agnandji","year":"2016","journal-title":"N Engl J Med"},{"key":"2021060106125076800_CIT0033","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1056\/NEJMoa1414216","article-title":"A recombinant vesicular stomatitis virus Ebola vaccine","volume":"376","author":"Regules","year":"2017","journal-title":"N Engl J Med"},{"key":"2021060106125076800_CIT0034","doi-asserted-by":"crossref","first-page":"4050","DOI":"10.1016\/j.vaccine.2020.03.015","article-title":"Arranging good clinical practices training and trial monitoring for a vaccine efficacy study during a public health emergency of international concern","volume":"38","author":"Tapia","year":"2020","journal-title":"Vaccine"},{"key":"2021060106125076800_CIT0035","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/S1473-3099(17)30541-8","article-title":"Ring vaccination with rVSV-ZEBOV under expanded access in response to an outbreak of Ebola virus disease in Guinea, 2016: an operational and vaccine safety report","volume":"17","author":"Gsell","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"2021060106125076800_CIT0036","doi-asserted-by":"crossref","first-page":"10178","DOI":"10.1073\/pnas.1817329116","article-title":"Ebola vaccination in the Democratic Republic of the Congo","volume":"116","author":"Wells","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2021060106125076800_CIT0037","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.1001\/jama.2020.8711","article-title":"Planning for a COVID-19 vaccination program","volume":"323","author":"Schaffer","year":"2020","journal-title":"JAMA"},{"key":"2021060106125076800_CIT0038","doi-asserted-by":"crossref","first-page":"603","DOI":"10.4269\/ajtmh.20-0654","article-title":"Threat of COVID-19 vaccine hesitancy in Pakistan: the need for measures to neutralize misleading narratives","volume":"103","author":"Khan","year":"2020","journal-title":"Am J Trop Med Hyg"},{"key":"2021060106125076800_CIT0039","doi-asserted-by":"crossref","first-page":"m2184","DOI":"10.1136\/bmj.m2184","article-title":"Even covid-19 can\u2019t kill the anti-vaccination movement","volume":"369","author":"Megget","year":"2020","journal-title":"BMJ"},{"key":"2021060106125076800_CIT0040","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1093\/infdis\/jiaa314","article-title":"Severe acute respiratory syndrome coronavirus 2 human challenge trials: too risky, too soon","volume":"222","author":"Dawson","year":"2020","journal-title":"J Infect Dis"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciaa1290\/36246518\/ciaa1290.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/cid\/article-pdf\/72\/11\/2035\/38389506\/ciaa1290.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/cid\/article-pdf\/72\/11\/2035\/38389506\/ciaa1290.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T08:07:42Z","timestamp":1622534862000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/72\/11\/2035\/5898660"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,28]]},"references-count":40,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,8,28]]},"published-print":{"date-parts":[[2021,6,1]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciaa1290","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,6,1]]},"published":{"date-parts":[[2020,8,28]]}}}