{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:38:14Z","timestamp":1792791494679,"version":"4.5.0"},"reference-count":48,"publisher":"Elsevier BV","issue":"10","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Institutes of Health National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012802","name":"Ragon Institute of Mass General MIT and Harvard","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012802","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Gates Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1016\/j.ymthe.2025.07.036","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T16:21:36Z","timestamp":1753806096000},"page":"4858-4873","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"title":["Augmented humoral responses to HIV Env trimers delivered as transmembrane immunogens by self-replicating RNA"],"prefix":"10.1016","volume":"33","author":[{"given":"Parisa","family":"Yousefpour","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amrit Raj","family":"Ghosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Himanshi","family":"Chawla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Yeung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Gregory","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Si","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanaka K.","family":"Remba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen A.","family":"Rodrigues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariane B.","family":"Melo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Dye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon M.","family":"Steichen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuebao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhou","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Crispin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Schief","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Facundo D.","family":"Batista","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8637-1405","authenticated-orcid":false,"given":"Darrell J.","family":"Irvine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymthe.2025.07.036_bib1","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1038\/s41573-021-00283-5","article-title":"mRNA vaccines for infectious diseases: principles, delivery and clinical translation","volume":"20","author":"Chaudhary","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ymthe.2025.07.036_bib2","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1038\/s41587-022-01294-2","article-title":"The clinical progress of mRNA vaccines and immunotherapies","volume":"40","author":"Barbier","year":"2022","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2025.07.036_bib3","doi-asserted-by":"crossref","DOI":"10.3389\/fmicb.2022.845625","article-title":"The emerging role of RNA modifications in the regulation of antiviral innate immunity","volume":"13","author":"Tong","year":"2022","journal-title":"Front. Microbiol."},{"key":"10.1016\/j.ymthe.2025.07.036_bib4","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/s12276-020-0407-z","article-title":"The emerging role of RNA modifications in the regulation of mRNA stability","volume":"52","author":"Boo","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"10.1016\/j.ymthe.2025.07.036_bib5","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/j.tibtech.2023.05.007","article-title":"Rise of the RNA machines \u2013 self-amplification in mRNA vaccine design","volume":"41","author":"Comes","year":"2023","journal-title":"Trends Biotechnol."},{"key":"10.1016\/j.ymthe.2025.07.036_bib6","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/s41434-020-00204-y","article-title":"Self-amplifying RNA vaccines for infectious diseases","volume":"28","author":"Bloom","year":"2021","journal-title":"Gene Ther."},{"key":"10.1016\/j.ymthe.2025.07.036_bib7","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3390\/vaccines9020097","article-title":"An update on self-amplifying mRNA vaccine development","volume":"9","author":"Blakney","year":"2021","journal-title":"Vaccines"},{"key":"10.1016\/j.ymthe.2025.07.036_bib8","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1038\/s41591-024-02955-2","article-title":"An Omicron-specific, self-amplifying mRNA booster vaccine for COVID-19: a phase 2\/3 randomized trial","volume":"30","author":"Saraf","year":"2024","journal-title":"Nat. Med."},{"key":"10.1016\/j.ymthe.2025.07.036_bib9","doi-asserted-by":"crossref","first-page":"14604","DOI":"10.1073\/pnas.1209367109","article-title":"Nonviral delivery of self-amplifying RNA vaccines","volume":"109","author":"Geall","year":"2012","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.ymthe.2025.07.036_bib10","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.ymthe.2017.11.017","article-title":"Self-amplifying RNA vaccines give equivalent protection against influenza to mRNA vaccines but at much lower doses","volume":"26","author":"Vogel","year":"2018","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2025.07.036_bib11","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1038\/s41467-025-55843-9","article-title":"Safety and immunogenicity of an optimized self-replicating RNA platform for low dose or single dose vaccine applications: a randomized, open label Phase I study in healthy volunteers","volume":"16","author":"Maine","year":"2025","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2025.07.036_bib12","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/S1473-3099(24)00060-4","article-title":"Persistence of immune responses of a self-amplifying RNA COVID-19 vaccine (ARCT-154) versus BNT162b2","volume":"24","author":"Oda","year":"2024","journal-title":"Lancet Infect. Dis."},{"key":"10.1016\/j.ymthe.2025.07.036_bib13","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1010885","article-title":"Enhanced immune responses following heterologous vaccination with self-amplifying RNA and mRNA COVID-19 vaccines","volume":"18","author":"Elliott","year":"2022","journal-title":"Plos Pathog."},{"key":"10.1016\/j.ymthe.2025.07.036_bib14","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1016\/j.immuni.2022.09.003","article-title":"Membrane-bound mRNA immunogens lower the threshold to activate HIV Env V2 apex-directed broadly neutralizing B cell precursors in humanized mice","volume":"55","author":"Melzi","year":"2022","journal-title":"Immunity"},{"key":"10.1016\/j.ymthe.2025.07.036_bib15","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.omtn.2021.06.008","article-title":"Immunogenicity of stabilized HIV-1 Env trimers delivered by self-amplifying mRNA","volume":"25","author":"Aldon","year":"2021","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"10.1016\/j.ymthe.2025.07.036_bib16","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1038\/s43018-020-0095-6","article-title":"Multifunctional oncolytic nanoparticles deliver self-replicating IL-12 RNA to eliminate established tumors and prime systemic immunity","volume":"1","author":"Li","year":"2020","journal-title":"Nat. Cancer"},{"key":"10.1016\/j.ymthe.2025.07.036_bib17","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1016\/j.ymthe.2019.08.007","article-title":"Immunogenicity of RNA replicons encoding HIV Env immunogens designed for self-assembly into nanoparticles","volume":"27","author":"Melo","year":"2019","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2025.07.036_bib18","doi-asserted-by":"crossref","DOI":"10.1126\/science.aax4380","article-title":"A generalized HIV vaccine design strategy for priming of broadly neutralizing antibody responses","volume":"366","author":"Steichen","year":"2019","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2025.07.036_bib19","doi-asserted-by":"crossref","first-page":"236ra63","DOI":"10.1126\/scitranslmed.3008104","article-title":"Promiscuous glycan site recognition by antibodies to the high-mannose patch of gp120 broadens neutralization of HIV","volume":"6","author":"Sok","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ymthe.2025.07.036_bib20","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1016\/j.immuni.2022.09.001","article-title":"Human immunoglobulin repertoire analysis guides design of vaccine priming immunogens targeting HIV V2-apex broadly neutralizing antibody precursors","volume":"55","author":"Willis","year":"2022","journal-title":"Immunity"},{"key":"10.1016\/j.ymthe.2025.07.036_bib21","doi-asserted-by":"crossref","first-page":"2695","DOI":"10.1016\/j.celrep.2016.02.058","article-title":"Composition and antigenic effects of individual glycan sites of a trimeric HIV-1 envelope glycoprotein","volume":"14","author":"Behrens","year":"2016","journal-title":"Cell Rep."},{"key":"10.1016\/j.ymthe.2025.07.036_bib22","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1002\/bit.26498","article-title":"cGMP production and analysis of BG505 SOSIP.664, an extensively glycosylated, trimeric HIV-1 envelope glycoprotein vaccine candidate","volume":"115","author":"Dey","year":"2018","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymthe.2025.07.036_bib23","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1016\/j.celrep.2018.07.080","article-title":"Site-specific glycosylation of virion-derived HIV-1 Env is mimicked by a soluble trimeric immunogen","volume":"24","author":"Struwe","year":"2018","journal-title":"Cell Rep."},{"key":"10.1016\/j.ymthe.2025.07.036_bib24","doi-asserted-by":"crossref","first-page":"e01894-16","DOI":"10.1128\/JVI.01894-16","article-title":"Molecular architecture of the cleavage-dependent mannose patch on a soluble HIV-1 envelope glycoprotein trimer","volume":"91","author":"Behrens","year":"2017","journal-title":"J. Virol."},{"key":"10.1016\/j.ymthe.2025.07.036_bib25","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/nature10373","article-title":"Broad neutralization coverage of HIV by multiple highly potent antibodies","volume":"477","author":"Walker","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2025.07.036_bib26","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.sbi.2017.03.008","article-title":"Structural principles controlling HIV envelope glycosylation","volume":"44","author":"Behrens","year":"2017","journal-title":"Curr. Opin. Struct. Biol."},{"key":"10.1016\/j.ymthe.2025.07.036_bib27","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/nature10696","article-title":"Structure of HIV-1 gp120 V1\/V2 domain with broadly neutralizing antibody PG9","volume":"480","author":"McLellan","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2025.07.036_bib28","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/nrd.2017.243","article-title":"mRNA vaccines \u2014 a new era in vaccinology","volume":"17","author":"Pardi","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ymthe.2025.07.036_bib29","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1146\/annurev-immunol-041015-055515","article-title":"Broadly neutralizing antibodies to HIV and their role in vaccine design","volume":"34","author":"Burton","year":"2016","journal-title":"Annu. Rev. Immunol."},{"key":"10.1016\/j.ymthe.2025.07.036_bib30","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.4049\/jimmunol.1901051","article-title":"HIV-1 gp120\u2013CD4-induced antibody complex elicits CD4 binding site\u2013specific antibody response in mice","volume":"204","author":"Galkin","year":"2020","journal-title":"J. Immunol."},{"key":"10.1016\/j.ymthe.2025.07.036_bib31","doi-asserted-by":"crossref","DOI":"10.1126\/science.adk0582","article-title":"mRNA-LNP HIV-1 trimer boosters elicit precursors to broad neutralizing antibodies","volume":"384","author":"Xie","year":"2024","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2025.07.036_bib32","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41541-021-00307-6","article-title":"Lipid nanoparticle encapsulated nucleoside-modified mRNA vaccines elicit polyfunctional HIV-1 antibodies comparable to proteins in nonhuman primates","volume":"6","author":"Saunders","year":"2021","journal-title":"npj Vaccin."},{"key":"10.1016\/j.ymthe.2025.07.036_bib33","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2022.110514","article-title":"mRNA-encoded HIV-1 Env trimer ferritin nanoparticles induce monoclonal antibodies that neutralize heterologous HIV-1 isolates in mice","volume":"38","author":"Mu","year":"2022","journal-title":"Cell Rep."},{"key":"10.1016\/j.ymthe.2025.07.036_bib34","doi-asserted-by":"crossref","first-page":"2810","DOI":"10.1038\/s41467-023-38457-x","article-title":"saRNA vaccine expressing membrane-anchored RBD elicits broad and durable immunity against SARS-CoV-2 variants of concern","volume":"14","author":"Komori","year":"2023","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2025.07.036_bib35","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1038\/s41422-021-00531-8","article-title":"Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2","volume":"31","author":"Sun","year":"2021","journal-title":"Cell Res."},{"key":"10.1016\/j.ymthe.2025.07.036_bib36","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1080\/19420862.2017.1323159","article-title":"Affinity of human IgG subclasses to mouse Fc gamma receptors","volume":"9","author":"Dekkers","year":"2017","journal-title":"mAbs"},{"key":"10.1016\/j.ymthe.2025.07.036_bib37","doi-asserted-by":"crossref","DOI":"10.1080\/19420862.2021.1882028","article-title":"Coming together at the hinges: Therapeutic prospects of IgG3","volume":"13","author":"Chu","year":"2021","journal-title":"mAbs"},{"key":"10.1016\/j.ymthe.2025.07.036_bib38","doi-asserted-by":"crossref","first-page":"3372","DOI":"10.4049\/jimmunol.159.7.3372","article-title":"Flexibility of human IgG subclasses","volume":"159","author":"Roux","year":"1997","journal-title":"J. Immunol."},{"key":"10.1016\/j.ymthe.2025.07.036_bib39","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.0040320","article-title":"Long-term clinical protection from Falciparum Malaria is strongly associated with IgG3 antibodies to Merozoite surface protein 3","volume":"4","author":"Roussilhon","year":"2007","journal-title":"Plos Med."},{"key":"10.1016\/j.ymthe.2025.07.036_bib40","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1093\/infdis\/jis033","article-title":"Early appearance of neutralizing immunoglobulin G3 antibodies is associated with Chikungunya virus clearance and long-term clinical protection","volume":"205","author":"Kam","year":"2012","journal-title":"J. Infect. Dis."},{"key":"10.1016\/j.ymthe.2025.07.036_bib41","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3007730","article-title":"Vaccine-induced Env V1-V2 IgG3 correlates with lower HIV-1 infection risk and declines soon after vaccination","volume":"6","author":"Yates","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ymthe.2025.07.036_bib42","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.733958","article-title":"HIV broadly neutralizing antibodies expressed as IgG3 preserve neutralization potency and show improved Fc effector function","volume":"12","author":"Richardson","year":"2021","journal-title":"Front. Immunol."},{"key":"10.1016\/j.ymthe.2025.07.036_bib43","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.abq5096","article-title":"B cell responses to membrane-presented antigens require the function of the mechanosensitive cation channel Piezo1","volume":"16","author":"Kwak","year":"2023","journal-title":"Sci. Signal."},{"key":"10.1016\/j.ymthe.2025.07.036_bib44","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/nbt.3301","article-title":"Mammalian synthetic circuits with RNA binding proteins for RNA-only delivery","volume":"33","author":"Wroblewska","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2025.07.036_bib45","doi-asserted-by":"crossref","first-page":"8099","DOI":"10.1021\/acs.nanolett.5b03528","article-title":"An orthogonal array optimization of lipid-like nanoparticles for mRNA delivery in vivo","volume":"15","author":"Li","year":"2015","journal-title":"Nano Lett."},{"key":"10.1016\/j.ymthe.2025.07.036_bib46","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.abf1152","article-title":"A particulate saponin\/TLR agonist vaccine adjuvant alters lymph flow and modulates adaptive immunity","volume":"6","author":"Silva","year":"2021","journal-title":"Sci. Immunol."},{"key":"10.1016\/j.ymthe.2025.07.036_bib47","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1126\/science.1187659","article-title":"Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1","volume":"329","author":"Wu","year":"2010","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2025.07.036_bib48","doi-asserted-by":"crossref","DOI":"10.15252\/embj.201899243","article-title":"One-step CRISPR\/Cas9 method for the rapid generation of human antibody heavy chain knock-in mice","volume":"37","author":"Lin","year":"2018","journal-title":"EMBO J."}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001625005726?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001625005726?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:47:24Z","timestamp":1792788444000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001625005726"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":48,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["S1525001625005726"],"URL":"https:\/\/doi.org\/10.1016\/j.ymthe.2025.07.036","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Augmented humoral responses to HIV Env trimers delivered as transmembrane immunogens by self-replicating RNA","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymthe.2025.07.036","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy.","name":"copyright","label":"Copyright"}]}}