{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:02:21Z","timestamp":1792839741045,"version":"4.5.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"1","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI158666"],"award-info":[{"award-number":["R01AI158666"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Food and Drug Administration program","award":["Z01 BK 04010-18LHV"],"award-info":[{"award-number":["Z01 BK 04010-18LHV"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Global elimination of chronic hepatitis C (CHC) remains difficult without an effective vaccine. Since injection drug use is the leading cause of hepatitis C virus (HCV) transmission in Western Europe and North America, people who inject drugs (PWID) are an important population for testing HCV vaccine effectiveness in randomized-clinical trials (RCTs). However, RCTs in PWID are inherently challenging. To accelerate vaccine development, controlled human infection (CHI) models have been suggested as a means to identify effective vaccines. To bridge the gap between CHI models and real-world testing, we developed an agent-based model simulating a two-dose vaccine to prevent CHC in PWID, representing 32,000 PWID in metropolitan Chicago and accounting for networks and HCV infections. We ran 500 trial simulations under 50 and 75% assumed vaccine efficacy (aVE) and sampled HCV infection status of recruited in silico PWID. The mean estimated vaccine efficacy (eVE) for 50 and 75% aVE was 48% (SD \u00b1 12) and 72% (SD \u00b1 11), respectively. For both conditions, the majority of trials (\u223c71%) resulted in eVEs within 1 SD of the mean, demonstrating a robust trial design. Trials that resulted in eVEs &amp;gt;1 SD from the mean (lowest eVEs of 3 and 35% for 50 and 75% aVE, respectively), were more likely to have imbalances in acute infection rates across trial arms. Modeling indicates robust trial design and high success rates of finding vaccines to be effective in real-life trials in PWID. However, with less effective vaccines (aVEs\u223c50%) there remains a higher risk of concluding poor vaccine efficacy due to post-randomization imbalances.<\/jats:p>","DOI":"10.1093\/pnasnexus\/pgae564","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T07:04:22Z","timestamp":1734505462000},"source":"Crossref","is-referenced-by-count":3,"title":["Modeling of randomized hepatitis C vaccine trials: Bridging the gap between controlled human infection models and real-word testing"],"prefix":"10.1093","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7238-5240","authenticated-orcid":false,"given":"Mary-Ellen","family":"Mackesy-Amiti","sequence":"first","affiliation":[{"name":"Division of Community Health Sciences, School of Public Health, University of Illinois at Chicago , Chicago, IL 60612 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3324-2220","authenticated-orcid":false,"given":"Alexander","family":"Gutfraind","sequence":"additional","affiliation":[{"name":"The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Chicago , Maywood, IL 60153 ,","place":["USA"]},{"name":"Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago , Chicago, IL 60612 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7927-4255","authenticated-orcid":false,"given":"Eric","family":"Tatara","sequence":"additional","affiliation":[{"name":"Consortium for Advanced Science and Engineering, University of Chicago , Chicago, IL 60637 ,","place":["USA"]},{"name":"Decision and Infrastructure Sciences, Argonne National Laboratory , Lemont, IL 60439 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2376-4156","authenticated-orcid":false,"given":"Nicholson T","family":"Collier","sequence":"additional","affiliation":[{"name":"Consortium for Advanced Science and Engineering, University of Chicago , Chicago, IL 60637 ,","place":["USA"]},{"name":"Decision and Infrastructure Sciences, Argonne National Laboratory , Lemont, IL 60439 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott J","family":"Cotler","sequence":"additional","affiliation":[{"name":"The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Chicago , Maywood, IL 60153 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,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3686-8894","authenticated-orcid":false,"given":"Basmattee","family":"Boodram","sequence":"additional","affiliation":[{"name":"Division of Community Health Sciences, School of Public Health, University of Illinois at Chicago , Chicago, IL 60612 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0874-359X","authenticated-orcid":false,"given":"Marian","family":"Major","sequence":"additional","affiliation":[{"name":"Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration , Silver Spring, MD 20993 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3357-1817","authenticated-orcid":false,"given":"Harel","family":"Dahari","sequence":"additional","affiliation":[{"name":"The Program for Experimental & Theoretical 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A review on spontaneous clearance of hepatitis C virus infection","volume":"16","author":"Rzymski","year":"2024","journal-title":"Viruses"},{"key":"2025012710312750200_pgae564-B31","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1053\/j.gastro.2009.09.017","article-title":"Spontaneous control of primary hepatitis C virus infection and immunity against persistent reinfection","volume":"138","author":"Osburn","year":"2010","journal-title":"Gastroenterology"},{"key":"2025012710312750200_pgae564-B32","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1093\/infdis\/jiv220","article-title":"Hepatitis C virus reinfection and spontaneous clearance of reinfection\u2014the InC3 study","volume":"212","author":"Sacks-Davis","year":"2015","journal-title":"J Infect Dis"},{"key":"2025012710312750200_pgae564-B33","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1053\/j.gastro.2010.05.077","article-title":"Meta-analysis of hepatitis C virus vaccine efficacy in chimpanzees indicates an importance for structural proteins","volume":"139","author":"Dahari","year":"2010","journal-title":"Gastroenterology"},{"key":"2025012710312750200_pgae564-B34","doi-asserted-by":"crossref","first-page":"7544","DOI":"10.1016\/j.vaccine.2015.09.099","article-title":"Vaccine approaches to malaria control and elimination: insights from mathematical models","volume":"33","author":"White","year":"2015","journal-title":"Vaccine"},{"key":"2025012710312750200_pgae564-B35","doi-asserted-by":"crossref","first-page":"e0264983","DOI":"10.1371\/journal.pone.0264983","article-title":"Modeling hepatitis C micro-elimination among people who inject drugs with direct-acting antivirals in metropolitan Chicago","volume":"17","author":"Tatara","year":"2022","journal-title":"PLoS One"},{"key":"2025012710312750200_pgae564-B36","author":"Ozik","year":"2016"}],"container-title":["PNAS Nexus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/pnasnexus\/advance-article-pdf\/doi\/10.1093\/pnasnexus\/pgae564\/61220199\/pgae564.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/pnasnexus\/article-pdf\/4\/1\/pgae564\/61220199\/pgae564.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/pnasnexus\/article-pdf\/4\/1\/pgae564\/61220199\/pgae564.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T10:31:53Z","timestamp":1737973913000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/pnasnexus\/article\/doi\/10.1093\/pnasnexus\/pgae564\/7927175"}},"subtitle":[],"editor":[{"given":"David","family":"Brenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,12,18]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,12,23]]}},"URL":"https:\/\/doi.org\/10.1093\/pnasnexus\/pgae564","relation":{},"ISSN":["2752-6542"],"issn-type":[{"value":"2752-6542","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,1]]},"published":{"date-parts":[[2024,12,18]]},"article-number":"pgae564"}}