{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:42:02Z","timestamp":1789497722669,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013039","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000}}],"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute for Health","award":["AI138212"],"award-info":[{"award-number":["AI138212"]}]},{"name":"National Institute of Health","award":["AI143370"],"award-info":[{"award-number":["AI143370"]}]},{"name":"National Institute of Health","award":["AI177095"],"award-info":[{"award-number":["AI177095"]}]},{"name":"National Institute of Health","award":["AI146028"],"award-info":[{"award-number":["AI146028"]}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","award":["HHSN272201800004C"],"award-info":[{"award-number":["HHSN272201800004C"]}],"id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","award":["HHSN272201800004C"],"award-info":[{"award-number":["HHSN272201800004C"]}],"id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Antibodies belonging to the VRC01-class display broad and potent neutralizing activities and have been isolated from several people living with HIV (PLWH). A member of that class, monoclonal antibody VRC01, was shown to reduce HIV-acquisition in two phase 2b efficacy trials. VRC01-class antibodies are therefore expected to be one component of an effective HIV-1 vaccine elicited response. In contrast to the VRC01-class antibodies that are highly mutated, their unmutated forms do not engage HIV-1 envelope (Env) and do not display neutralizing activities. Hence, specifically modified Env-derived proteins have been designed to engage the unmutated forms of VRC01-class antibodies, and to activate the corresponding na\u00efve B cells. Selected heterologous Env must then be used as boost immunogens to guide the proper maturation of these elicited VRC01-class antibodies. Here we examined whether and how the valency of the prime and boost immunogens influences VRC01-class antibody-maturation. Our findings indicate that, indeed the valency of the immunogen affects the maturation of elicited antibody responses by preferentially selecting VRC01-like antibodies that have accumulated somatic mutations present in broadly neutralizing VRC01-class antibodies isolated from PLWH. As a result, antibodies isolated from animals immunized with the higher valency immunogens display broader Env cross-binding properties and improved neutralizing potentials than those isolated from animals immunized with the lower valency immunogens. Our results are relevant to current and upcoming phase 1 clinical trials that evaluate the ability of novel immunogens aiming to elicit cross-reactive VRC01-class antibody responses.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013039","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T13:34:53Z","timestamp":1748525693000},"page":"e1013039","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Increased immunogen valency improves the maturation of vaccine-elicited HIV-1 VRC01-like antibodies"],"prefix":"10.1371","volume":"21","author":[{"given":"Parul","family":"Agrawal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arineh","family":"Khechaduri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey 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A.","family":"Matsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Montefiori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1106-7097","authenticated-orcid":true,"given":"Leonidas","family":"Stamatatos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,5,29]]},"reference":[{"issue":"5","key":"ppat.1013039.ref001","doi-asserted-by":"crossref","DOI":"10.1016\/S2352-3018(23)00051-6","article-title":"Long-acting antiretrovirals and HIV treatment adherence","volume":"10","author":"JB Nachega","year":"2023","journal-title":"Lancet 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Briney","year":"2016","journal-title":"Cell"},{"issue":"2","key":"ppat.1013039.ref039","doi-asserted-by":"crossref","DOI":"10.1016\/j.immuni.2020.12.014","article-title":"Vaccination induces maturation in a mouse model of diverse unmutated VRC01-class precursors to HIV-neutralizing antibodies with >50% breadth","volume":"54","author":"X Chen","year":"2021","journal-title":"Immunity"},{"issue":"8","key":"ppat.1013039.ref040","doi-asserted-by":"crossref","first-page":"3817","DOI":"10.1128\/IAI.01369-07","article-title":"The oligomerization domain of C4-binding protein (C4bp) acts as an adjuvant, and the fusion protein comprised of the 19-kilodalton merozoite surface protein 1 fused with the murine C4bp domain protects mice against malaria","volume":"76","author":"SA Ogun","year":"2008","journal-title":"Infect Immun"},{"issue":"8","key":"ppat.1013039.ref041","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1016\/j.jmb.2012.12.017","article-title":"Arranged sevenfold: structural 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