{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T17:08:05Z","timestamp":1786640885204,"version":"build-2736575974"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T00:00:00Z","timestamp":1757721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DMS-2347859"],"award-info":[{"award-number":["DMS-2347859"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1AI144371"],"award-info":[{"award-number":["UM1AI144371"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Duke Consortia for HIV\/AIDS Vaccine Development"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A key challenge in B-cell lineage\u2013based vaccine design is understanding the \u201cinducibility\u201d of target neutralizing antibodies\u2014the ability of these antibodies to be elicited by presentation of an immunogen. Induction relies on a combination of stochastic diversification and immunogen-based selection, and as a result is heavily dependent on the probabilistic accessibility of induction pathways. We explored inducibility using a detailed stochastic model of the somatic hypermutation process\u2014which captures the critical \u201ccontext-dependence\u201d of sequence mutation rates\u2014coupled to a stochastic population model for B-cell clonal maturation. The model is used to calculate inducibilities for a set of critical mutations required by the HIV broadly neutralizing antibody (bnAb) CH235.12. The results provide insight into barriers to the elicitation of HIV bnAbs and explain experimental results observed in mouse models. Our models enable detailed analysis of maturation pathway probabilities, allowing us to identify opportunities for the design of boosting immunogens aimed at elicitation of CH235.12 via a sequential vaccination regimen.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf234","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T19:08:19Z","timestamp":1758308899000},"source":"Crossref","is-referenced-by-count":1,"title":["Computing the inducibility of broadly neutralizing antibodies under a context-dependent model of affinity maturation: applications to sequential vaccine design"],"prefix":"10.1093","volume":"215","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3268-9652","authenticated-orcid":false,"given":"Joseph","family":"Mathews","sequence":"first","affiliation":[{"name":"Department of Statistical Science, Duke University , Durham, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Van Itallie","sequence":"additional","affiliation":[{"name":"Duke Human Vaccine Institute, Duke University School of Medicine , Durham, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongkang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Duke University , Durham, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9933-9618","authenticated-orcid":false,"given":"Kevin","family":"Wiehe","sequence":"additional","affiliation":[{"name":"Duke Human Vaccine Institute, Duke University School of Medicine , Durham, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3733-3716","authenticated-orcid":false,"given":"Scott C","family":"Schmidler","sequence":"additional","affiliation":[{"name":"Department of Statistical Science, Duke University , Durham, NC,","place":["United States"]},{"name":"Department of Computer Science, Duke University , Durham, NC,","place":["United States"]},{"name":"Program in Computational Biology and Bioinformatics, Duke University , Durham, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,13]]},"reference":[{"key":"2026013008270857700_vkaf234-B1","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/nri.2017.148","article-title":"Passive immunotherapy of viral infections: \u2018super-antibodies\u2019 enter the fray","volume":"18","author":"Walker","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"2026013008270857700_vkaf234-B2","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/s41577-022-00753-w","article-title":"Strategies for HIV-1 vaccines that induce broadly neutralizing antibodies","volume":"23","author":"Haynes","year":"2023","journal-title":"Nat Rev Immunol"},{"key":"2026013008270857700_vkaf234-B3","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1126\/science.aad9195","article-title":"HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen","volume":"351","author":"Jardine","year":"2016","journal-title":"Science"},{"key":"2026013008270857700_vkaf234-B4","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.chom.2018.04.018","article-title":"Functional relevance of improbable antibody mutations for HIV broadly neutralizing antibody development","volume":"23","author":"Wiehe","year":"2018","journal-title":"Cell Host Microbe"},{"key":"2026013008270857700_vkaf234-B5","doi-asserted-by":"crossref","DOI":"10.1126\/science.aay7199","article-title":"Targeted selection of HIV-specific antibody mutations by engineering B cell maturation","volume":"366","author":"Saunders","year":"2019","journal-title":"Science"},{"key":"2026013008270857700_vkaf234-B6","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/nbt.2197","article-title":"B-cell-lineage immunogen design in vaccine development with HIV-1 as a case study","volume":"30","author":"Haynes","year":"2012","journal-title":"Nat Biotechnol"},{"key":"2026013008270857700_vkaf234-B7","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1126\/science.aac5894","article-title":"HIV-1 VACCINES. 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