{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:59:05Z","timestamp":1788274745669,"version":"build-2803163510"},"reference-count":62,"publisher":"American Society for Clinical Investigation","issue":"16","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":46,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["Intramural Research Program"],"award-info":[{"award-number":["Intramural Research Program"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["1R01AI192628-01"],"award-info":[{"award-number":["1R01AI192628-01"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Gates Foundation","award":["INV-088153"],"award-info":[{"award-number":["INV-088153"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,17]]},"abstract":"<jats:p>BACKGROUND<\/jats:p>\n                  <jats:p>\n                    CIS43LS is a long-acting mAb that targets the\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    circumsporozoite protein. A phase II trial showed that a single dose of CIS43LS conferred &gt; 85% sterile protection against infection in Malian adults over 6 months. Understanding the pharmacokinetics and pharmacodynamics (PK\/PD) of CIS43LS is critical for the further development of CIS43LS and other antimalaria mAbs.\n                  <\/jats:p>\n                  <jats:p>METHODS<\/jats:p>\n                  <jats:p>Using 3,777 serum samples collected from 348 trial participants over the 6-month study period, we performed a PK\/PD analysis of CIS43LS that included assessments for antidrug antibodies and target-mediated drug disposition. A 2-compartment, nonlinear mixed effects population PK model that evaluated demographic, anthropometric, hematologic, baseline parasitemia, and endogenous IgG and IgG1 as potential covariates was used to estimate PK parameters and serum concentrations required to achieve 80% efficacy.<\/jats:p>\n                  <jats:p>RESULTS<\/jats:p>\n                  <jats:p>\n                    The median CIS43LS\n                    <jats:italic>\n                      t\n                      <jats:sub>1\/2<\/jats:sub>\n                    <\/jats:italic>\n                    was 63.2 days (95% CI, 59.4\u201367.2 days). Serum concentrations \u2265 64 \u03bcg\/mL (95% CI, 49\u201393 \u03bcg\/mL) corresponded to \u2265 80% efficacy against infection over 6 months. A simulated dose of 30 mg\/kg maintained serum concentrations &gt; 64 \u03bcg\/mL in &gt; 97.5% of individuals for 4 months, the time frame for the WHO preferred product characteristics for antimalaria mAbs. There was no evidence of antidrug antibodies. Among infected individuals who received CIS43LS, no marked evidence of target-mediated drug disposition was observed.\n                  <\/jats:p>\n                  <jats:p>CONCLUSION<\/jats:p>\n                  <jats:p>This study indicates that protective CIS43LS levels can be maintained over the course of a single malaria season and provides guidance for PK\/PD analyses of antimalaria mAbs in malaria-endemic populations.<\/jats:p>\n                  <jats:p>TRIAL REGISTRATION<\/jats:p>\n                  <jats:p>ClinicalTrials.gov NCT04329104.<\/jats:p>\n                  <jats:p>FUNDING<\/jats:p>\n                  <jats:p>NIH and Gates Foundation.<\/jats:p>\n                  <jats:p>Pharmacokinetic\/pharmacodynamic analyses of the long-acting anti-malaria monoclonal antibody CIS43LS demonstrate that protective antibody concentrations can be maintained in malaria-exposed adults over a single malaria season.<\/jats:p>","DOI":"10.1172\/jci207559","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T20:08:25Z","timestamp":1783368505000},"source":"Crossref","is-referenced-by-count":2,"title":["Pharmacokinetics and pharmacodynamics of a long-acting monoclonal antibody against malaria in African adults"],"prefix":"10.1172","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1928-861X","authenticated-orcid":true,"given":"Tuan M.","family":"Tran","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, and"},{"name":"Ryan White Center for Pediatric Infectious Disease and Global Health, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zonghui","family":"Hu","sequence":"additional","affiliation":[{"name":"Office of Biostatistics Research, National Institute of Allergy and Infectious Diseases, 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