{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T17:24:28Z","timestamp":1787073868261,"version":"build-2736575974"},"reference-count":23,"publisher":"American Chemical Society (ACS)","issue":"32","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"publisher","award":["N42A650180"],"award-info":[{"award-number":["N42A650180"]}],"id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Dengue virus (DENV) envelope protein domain III (EDIII) is a premier target for vaccine design because EDIII-specific antibodies can potently neutralize DENV with a low propensity for inducing antibody-dependent enhancement (ADE). We previously identified a cross-reactive antibody, R3N_2D3, which targets the EDIII AG-strand epitope and neutralizes all four DENV serotypes with low ADE, a desirable combination of activities among anti-DENV antibodies. In this study, we expanded this AG-strand-targeting antibody panel by identifying four additional anti-EDIII antibodies from our dengue-immune single-chain variable fragment (scFv)-phage libraries. Despite variations in their binding footprints, these new antibodies converged on key residues within the AG-strand epitope. When expressed as full IgG1, these candidates showed potent cross-neutralization with subnanomolar focus reduction neutralization titers (FRNT50 values) and consistently low ADE compared to the prototypical fusion-loop antibody 4G2 when tested in an in vitro U937 monocytic cell model. Collectively, these findings demonstrate that the AG-strand epitope can elicit broadly protective antibodies with reduced ADE risk, highlighting its potential as a strategic epitope for pan-DENV vaccine development.<\/jats:p>","DOI":"10.1021\/acsomega.6c02114","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T14:35:07Z","timestamp":1785854107000},"page":"47592-47601","source":"Crossref","is-referenced-by-count":0,"title":["Potent Cross-Serotype\nDengue Neutralization with Low\nADE by AG-Strand-Targeting Anti-EDIII Antibodies"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8067-7648","authenticated-orcid":true,"given":"Napon","family":"Nilchan","sequence":"first","affiliation":[{"name":"National Science and Technology Development Agency (NSTDA) , , , ,","place":["Khlong Nueng, Pathum Thani, Thailand, 12120"]},{"name":"Mahidol University , , ,","place":["Bangkok, Thailand, 10700"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anunyaporn","family":"Phungsom","sequence":"additional","affiliation":[{"name":"National Science and Technology Development Agency (NSTDA) , , , ,","place":["Khlong Nueng, Pathum Thani, Thailand, 12120"]},{"name":"Mahidol University , , ,","place":["Bangkok, Thailand, 10700"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9489-5798","authenticated-orcid":true,"given":"Mongkhonphan","family":"Tantiwatcharakunthon","sequence":"additional","affiliation":[{"name":"National Science and Technology Development Agency (NSTDA) , , , ,","place":["Khlong Nueng, Pathum Thani, Thailand, 12120"]},{"name":"Mahidol University , , ,","place":["Bangkok, Thailand, 10700"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasit","family":"Luangaram","sequence":"additional","affiliation":[{"name":"National Science and Technology Development Agency (NSTDA) , , , ,","place":["Khlong Nueng, Pathum Thani, Thailand, 12120"]},{"name":"Mahidol University , , ,","place":["Bangkok, Thailand, 10700"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pattarakul","family":"Pakchotanon","sequence":"additional","affiliation":[{"name":"National Science and Technology Development Agency (NSTDA) , , , ,","place":["Khlong Nueng, Pathum Thani, Thailand, 12120"]},{"name":"Mahidol University , , ,","place":["Bangkok, Thailand, 10700"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thaneeya","family":"Duangchinda","sequence":"additional","affiliation":[{"name":"National Science and Technology Development Agency (NSTDA) , , , ,","place":["Khlong Nueng, Pathum Thani, Thailand, 12120"]},{"name":"Mahidol University , , ,","place":["Bangkok, Thailand, 10700"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romchat","family":"Kraivong","sequence":"additional","affiliation":[{"name":"National Science and Technology Development Agency (NSTDA) , , , ,","place":["Khlong Nueng, Pathum Thani, Thailand, 12120"]},{"name":"Mahidol University , , ,","place":["Bangkok, Thailand, 10700"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanapan","family":"Prommool","sequence":"additional","affiliation":[{"name":"National Science and Technology Development Agency (NSTDA) , , , ,","place":["Khlong Nueng, Pathum Thani, Thailand, 12120"]},{"name":"Mahidol University , , ,","place":["Bangkok, Thailand, 10700"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chatchawan","family":"Srisawat","sequence":"additional","affiliation":[{"name":"Mahidol University , , ,","place":["Bangkok, Thailand, 10700"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunya","family":"Puttikhunt","sequence":"additional","affiliation":[{"name":"National Science and Technology Development Agency (NSTDA) , , , ,","place":["Khlong Nueng, Pathum Thani, Thailand, 12120"]},{"name":"Mahidol University , , ,","place":["Bangkok, Thailand, 10700"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"2026081810494726400_cit1","doi-asserted-by":"publisher","first-page":"1799","DOI":"10.3892\/mmr.2016.5454","article-title":"Functional Properties of DENV EDIII-Reactive Antibodies in Human\nDENV-1-Infected Sera and Rabbit Antiserum to EDIII","volume":"14","author":"Chen","year":"2016","journal-title":"Mol. Med. Rep."},{"issue":"6","key":"2026081810494726400_cit2","doi-asserted-by":"publisher","first-page":"470","DOI":"10.3390\/pathogens9060470","article-title":"Adaptive Immunity to Dengue Virus: Slippery Slope or\nSolid Ground for Rational Vaccine Design?","volume":"9","author":"Wilken","year":"2020","journal-title":"Pathogens"},{"key":"2026081810494726400_cit3","doi-asserted-by":"publisher","first-page":"4971","DOI":"10.4049\/jimmunol.1200227","article-title":"Structural\nAnalysis of a Dengue Cross-Reactive Antibody Complexed with Envelope\nDomain III Reveals the Molecular Basis of Cross-Reactivity","volume":"188","author":"Midgley","year":"2012","journal-title":"J. Immunol."},{"key":"2026081810494726400_cit4","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.str.2017.11.017","article-title":"Structural and Functional Characterization of a Cross-Reactive Dengue\nVirus Neutralizing Antibody that Recognizes a Cryptic Epitope","volume":"26","author":"Li","year":"2018","journal-title":"Structure"},{"key":"2026081810494726400_cit5","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1038\/s41590-018-0227-7","article-title":"Characterization of a Potent and\nHighly Unusual Minimally Enhancing Antibody Directed Against Dengue\nVirus","volume":"19","author":"Renner","year":"2018","journal-title":"Nat. Immunol."},{"key":"2026081810494726400_cit6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007836","article-title":"A Broadly Neutralizing\nGermline-Like Human Monoclonal Antibody Against Dengue Virus Envelope\nDomain III","volume":"15","author":"Hu","year":"2019","journal-title":"PLoS Pathog."},{"key":"2026081810494726400_cit7","doi-asserted-by":"publisher","first-page":"721","DOI":"10.3389\/fcimb.2020.572681","article-title":"Antibody-Dependent\nEnhancement: A Challenge for Developing a Safe Dengue Vaccine","volume":"10","author":"Shukla","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"2026081810494726400_cit8","doi-asserted-by":"publisher","first-page":"2393","DOI":"10.3390\/ijms24032393","article-title":"The Immunogenicity\nof DENV1\u20134 ED3s Strongly Differ Despite Their Almost Identical\nThree-Dimensional Structures and High Sequence Similarities","volume":"24","author":"Islam","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"2026081810494726400_cit9","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1099\/vir.0.055178-0","article-title":"Dengue\nVirus Envelope Domain III Immunization Elicits\nPredominantly Cross-Reactive, Poorly Neutralizing Antibodies Localized\nto the AB loop: Implications for Dengue Vaccine Design","volume":"94","author":"Li","year":"2013","journal-title":"J. Gen. Virol."},{"key":"2026081810494726400_cit10","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1021\/acscombsci.0c00073","article-title":"Combinatorial Resurfacing of Dengue\nEnvelope Protein Domain III Antigens Selectively Ablates Epitopes\nAssociated with Serotype-Specific or Infection-Enhancing Antibody\nResponses","volume":"22","author":"Remmel","year":"2020","journal-title":"ACS Comb. Sci."},{"key":"2026081810494726400_cit11","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1016\/j.chembiol.2022.02.004","article-title":"Resurfaced ZIKV EDIII Nanoparticle\nImmunogens Elicit\nNeutralizing and Protective Responses in Vivo","volume":"29","author":"Georgiev","year":"2022","journal-title":"Cell Chem. Biol."},{"key":"2026081810494726400_cit12","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2025.112534","article-title":"A Two-Component\nCocktail of Engineered\nDIII Nanoparticles Elicits Broadly Neutralizing Antibody Responses\nAgainst Dengue Virus in Mice","volume":"28","author":"Mariano","year":"2025","journal-title":"iScience"},{"key":"2026081810494726400_cit13","doi-asserted-by":"publisher","first-page":"12816","DOI":"10.1128\/JVI.00432-07","article-title":"Type- and Subcomplex-Specific Neutralizing Antibodies\nagainst Domain III of Dengue Virus Type 2 Envelope Protein Recognize\nAdjacent Epitopes","volume":"81","author":"Sukupolvi-Petty","year":"2007","journal-title":"J. Virol."},{"key":"2026081810494726400_cit14","doi-asserted-by":"publisher","first-page":"2690","DOI":"10.1021\/acsinfecdis.4c00058","article-title":"An Engineered\nN-Glycosylated Dengue Envelope Protein Domain III Facilitates Epitope-Directed\nSelection of Potently Neutralizing and Minimally Enhancing Antibodies","volume":"10","author":"Nilchan","year":"2024","journal-title":"ACS Infect. Dis."},{"key":"2026081810494726400_cit15","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1038\/nsmb.1382","article-title":"Binding\nof a Neutralizing Antibody to Dengue Virus Alters the Arrangement\nof Surface Glycoproteins","volume":"15","author":"Lok","year":"2008","journal-title":"Nat. Struct. Mol.\nBiol."},{"key":"2026081810494726400_cit16","doi-asserted-by":"publisher","first-page":"E1555","DOI":"10.1073\/pnas.1303645110","article-title":"Redesign of\na Cross-Reactive Antibody to Dengue Virus with Broad-Spectrum Activity\nand Increased in Vivo Potency","volume":"110","author":"Tharakaraman","year":"2013","journal-title":"Proc. Natl. Acad.\nSci. 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Natl. Acad. Sci. U.S.A."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.6c02114","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/32\/47592\/66360986\/acsomega.6c02114.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/32\/47592\/66360986\/acsomega.6c02114.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:26:27Z","timestamp":1787070387000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/11\/32\/47592\/5238641\/Potent-Cross-Serotype-Dengue-Neutralization-with"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,3]]},"references-count":23,"journal-issue":{"issue":"32","published-online":{"date-parts":[[2026,8,3]]},"published-print":{"date-parts":[[2026,8,18]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.6c02114","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,3]]}}}