{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T21:09:27Z","timestamp":1774559367515,"version":"3.50.1"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T00:00:00Z","timestamp":1650412800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006227","name":"Lawrence Livermore National Laboratory","doi-asserted-by":"publisher","award":["Grant 17-ERD-043 LLC Award B620960"],"award-info":[{"award-number":["Grant 17-ERD-043 LLC Award B620960"]}],"id":[{"id":"10.13039\/100006227","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012802","name":"Ragon Institute of MGH, MIT and Harvard","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012802","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CHARMM Development Project"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>The design of vaccines against highly mutable pathogens, such as HIV and influenza, requires a detailed understanding of how the adaptive immune system responds to encountering multiple variant antigens (Ags). Here, we describe a multiscale model of B cell receptor (BCR) affinity maturation that employs actual BCR nucleotide sequences and treats BCR\/Ag interactions in atomistic detail. We apply the model to simulate the maturation of a broadly neutralizing Ab (bnAb) against HIV. Starting from a germline precursor sequence of the VRC01 anti-HIV Ab, we simulate BCR evolution in response to different vaccination protocols and different Ags, which were previously designed by us. The simulation results provide qualitative guidelines for future vaccine design and reveal unique insights into bnAb evolution against the CD4 binding site of HIV. Our model makes possible direct comparisons of simulated BCR populations with results of deep sequencing data, which will be explored in future applications.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1009391","type":"journal-article","created":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T17:34:54Z","timestamp":1650476094000},"page":"e1009391","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Multiscale affinity maturation simulations to elicit broadly neutralizing antibodies against HIV"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7986-567X","authenticated-orcid":true,"given":"Simone","family":"Conti","sequence":"first","affiliation":[]},{"given":"Victor","family":"Ovchinnikov","sequence":"additional","affiliation":[]},{"given":"Jonathan G.","family":"Faris","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1268-9602","authenticated-orcid":true,"given":"Arup K.","family":"Chakraborty","sequence":"additional","affiliation":[]},{"given":"Martin","family":"Karplus","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7505-7920","authenticated-orcid":true,"given":"Kayla G.","family":"Sprenger","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2022,4,20]]},"reference":[{"key":"pcbi.1009391.ref001","unstructured":"UNAIDS Data 2018 | HIV\/AIDS Data Hub for the Asia-Pacific Region. [Cited 2021 Aug 4]. Available from: https:\/\/www.aidsdatahub.org\/resource\/unaids-data-2018."},{"key":"pcbi.1009391.ref002","unstructured":"Influenza (Seasonal). [Cited 2021 Aug 4]. Available from: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/influenza-(seasonal)."},{"key":"pcbi.1009391.ref003","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1093\/nar\/gkt1083","article-title":"BNAber: Database of broadly neutralizing HIV antibodies","volume":"42","author":"AM Eroshkin","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1009391.ref004","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.coviro.2017.03.002","article-title":"Tackling influenza with broadly neutralizing antibodies.","volume":"24","author":"D Corti","year":"2017","journal-title":"Curr Opin Virol"},{"key":"pcbi.1009391.ref005","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1146\/annurev-immunol-020711-075032","article-title":"Germinal centers.","volume":"30","author":"GD Victora","year":"2012","journal-title":"Annu Rev Immunol"},{"key":"pcbi.1009391.ref006","doi-asserted-by":"crossref","first-page":"E7039","DOI":"10.1073\/pnas.1614940113","article-title":"Optimal immunization cocktails can promote induction of broadly neutralizing Abs against highly mutable pathogens","volume":"113","author":"JS Shaffer","year":"2016","journal-title":"Proc Natl Acad Sci"},{"key":"pcbi.1009391.ref007","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.cell.2015.01.027","article-title":"Manipulating the selection forces during affinity maturation to generate cross-reactive HIV antibodies","volume":"160","author":"S Wang","year":"2015","journal-title":"Cell"},{"key":"pcbi.1009391.ref008","doi-asserted-by":"crossref","first-page":"20077","DOI":"10.1073\/pnas.1919329117","article-title":"Optimizing immunization protocols to elicit broadly neutralizing antibodies","volume":"117","author":"KG Sprenger","year":"2020","journal-title":"Proc Natl Acad Sci"},{"key":"pcbi.1009391.ref009","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.4049\/jimmunol.1600411","article-title":"A Stochastic model of the germinal center integrating local antigen competition, individualistic T\u2013B interactions, and B cell receptor signaling","volume":"197","author":"P Wang","year":"2016","journal-title":"J Immunol"},{"key":"pcbi.1009391.ref010","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.4049\/jimmunol.1401054","article-title":"Simulation of B cell affinity maturation explains enhanced antibody cross-reactivity induced by the polyvalent malaria vaccine AMA1","volume":"193","author":"S Chaudhury","year":"2014","journal-title":"J Immunol"},{"key":"pcbi.1009391.ref011","doi-asserted-by":"crossref","first-page":"e1005336","DOI":"10.1371\/journal.pcbi.1005336","article-title":"Optimal sequential immunization can focus antibody responses against diversity loss and distraction.","volume":"13","author":"S. 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