{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:25:43Z","timestamp":1787495143382,"version":"build-2736575974"},"reference-count":44,"publisher":"American Society for Clinical Investigation","issue":"7","license":[{"start":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T00:00:00Z","timestamp":1712534400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,8]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Broadly neutralizing monoclonal antibodies (bNAbs) represent a promising strategy for HIV-1 immunoprophylaxis and treatment. 10E8VLS and VRC07-523LS are bNAbs that target the highly conserved membrane-proximal external region (MPER) and the CD4-binding site of the HIV-1 viral envelope glycoprotein, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>In this phase 1, open-label trial, we evaluated the safety and pharmacokinetics of 5 mg\/kg 10E8VLS administered alone, or concurrently with 5 mg\/kg VRC07-523LS, via s.c. injection to healthy non\u2013HIV-infected individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Eight participants received either 10E8VLS alone (\n                      <jats:italic>n<\/jats:italic>\n                      = 6) or 10E8VLS and VRC07-523LS in combination (\n                      <jats:italic>n<\/jats:italic>\n                      = 2). Five (\n                      <jats:italic>n<\/jats:italic>\n                      = 5 of 8, 62.5%) participants who received 10E8VLS experienced moderate local reactogenicity, and 1 participant (\n                      <jats:italic>n<\/jats:italic>\n                      = 1\/8, 12.5%) experienced severe local reactogenicity. Further trial enrollment was stopped, and no participant received repeat dosing. All local reactogenicity resolved without sequelae. 10E8VLS retained its neutralizing capacity, and no functional anti-drug antibodies were detected; however, a serum\n                      <jats:italic>\n                        t\n                        <jats:sub>1\/2<\/jats:sub>\n                      <\/jats:italic>\n                      of 8.1 days was shorter than expected. Therefore, the trial was voluntarily stopped per sponsor decision (Vaccine Research Center, National Institute of Allergy and Infectious Diseases [NIAID], NIH). Mechanistic studies performed to investigate the underlying reason for the reactogenicity suggest that multiple mechanisms may have contributed, including antibody aggregation and upregulation of local inflammatory markers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      10E8VLS resulted in unexpected reactogenicity and a shorter\n                      <jats:italic>\n                        t\n                        <jats:sub>1\/2<\/jats:sub>\n                      <\/jats:italic>\n                      in comparison with previously tested bNAbs. These studies may facilitate identification of nonreactogenic second-generation MPER-targeting bNAbs, which could be an effective strategy for HIV-1 immunoprophylaxis and treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>Clinicaltrials.gov, accession no. NCT03565315.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci.insight.175375","type":"journal-article","created":{"date-parts":[[2024,4,7]],"date-time":"2024-04-07T14:00:31Z","timestamp":1712498431000},"source":"Crossref","is-referenced-by-count":9,"title":["Phase 1 trial evaluating safety and pharmacokinetics of HIV-1 broadly neutralizing mAbs 10E8VLS and VRC07-523LS"],"prefix":"10.1172","volume":"9","author":[{"given":"Seemal F.","family":"Awan","sequence":"first","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 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