{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T07:44:25Z","timestamp":1775979865427,"version":"3.50.1"},"posted":{"date-parts":[[2025,3,19]]},"group-title":"Immunology","reference-count":71,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The human immune system is intrinsically variable and remarkably diverse across a population. The immune response to antigens is driven by a complex interplay of time-dependent interdependencies across components of the immune system. After repeated vaccination, the humoral and cellular arms of the immune response display highly heterogeneous dynamics, further complicating the attribution of a phenotypic outcome to specific immune system components. We employ a random forest (RF) approach to classify informative differences in immunogenicity between older people living with HIV (PLWH) on ART and an age-matched control group who received up to five SARS-CoV-2 vaccinations over\n                  <jats:bold>104<\/jats:bold>\n                  weeks. RFs identify immunological variables of importance, interpreted as evidence for Th1 imprinting, and suggest novel distinguishing immune features, such as saliva-based antibody screening, as promising diagnostic features towards classifying responses (whereas serum IgG is not). Additionally, we implement supervised and unsupervised\n                  <jats:italic>Machine Learning<\/jats:italic>\n                  methods to produce physiologically accurate synthetic datasets that conform to the statistical distribution of the original immunological data, thus enabling further data-driven hypothesis testing and model validation. Our results highlight the effectiveness of RFs in utilizing informative immune feature interdependencies for classification tasks and suggests broad impacts of ML applications for personalized vaccination strategies among high-risk populations.\n                <\/jats:p>","DOI":"10.1101\/2025.03.18.643769","type":"posted-content","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T23:05:45Z","timestamp":1742598345000},"source":"Crossref","is-referenced-by-count":0,"title":["Machine Learning Reveals Distinct Immunogenic Signatures of Th1 Imprinting in ART-Treated Individuals with HIV Following Repeated SARS-CoV-2 Vaccination"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5137-2195","authenticated-orcid":false,"given":"Chapin S.","family":"Korosec","sequence":"first","affiliation":[{"name":"Modelling Infection and Immunity Lab, Mathematics and Statistics, York University, 4700 Keele St, Toronto, M3J 1P3, ON, Canada"},{"name":"Centre for Disease Modelling, Mathematics and Statistics, York University, 4700 Keele St, Toronto, M3J 1P3, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica M.","family":"Conway","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Pennsylvania State University, 201 Old Main, University Park, University Park, 16802, Pennsylvania, United States of America"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vitaliy A.","family":"Matveev","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toronto, 27 King\u2019s College Cir, Toronto, M5S 1A8, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7369-1936","authenticated-orcid":false,"given":"Mario","family":"Ostrowski","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toronto, 27 King\u2019s College Cir, Toronto, M5S 1A8, Ontario, Canada"},{"name":"Department of Immunology, University of Toronto, 1 King\u2019s College Cir, Toronto, M5S 1A8, Ontario, Canada"},{"name":"Keenan Research Centre for Biomedical Science, St. Michael\u2019s Hospital, Unity Health, Toronto, M5B 1W8, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane M.","family":"Heffernan","sequence":"additional","affiliation":[{"name":"Modelling Infection and Immunity Lab, Mathematics and Statistics, York University, 4700 Keele St, Toronto, M3J 1P3, ON, Canada"},{"name":"Centre for Disease Modelling, Mathematics and Statistics, York University, 4700 Keele St, Toronto, M3J 1P3, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4742-0726","authenticated-orcid":false,"given":"Mohammad Sajjad","family":"Ghaemi","sequence":"additional","affiliation":[{"name":"Digital Technologies Research Centre, National Research Council Canada, 222 College Street, Toronto, M5T 3J1, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041123563879000_2025.03.18.643769v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-023-00452-3"},{"key":"2026041123563879000_2025.03.18.643769v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(24)00212-1"},{"key":"2026041123563879000_2025.03.18.643769v1.3","doi-asserted-by":"publisher","DOI":"10.1111\/hiv.12421"},{"key":"2026041123563879000_2025.03.18.643769v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.35"},{"issue":"3","key":"2026041123563879000_2025.03.18.643769v1.5","first-page":"155","article-title":"Failure of CD4+ T-cell Recovery upon Virally-Effective cART: an Enduring Gap in the Understanding of HIV+ Immunological non-Responders","volume":"45","year":"2022","journal-title":"New Microbiologica"},{"key":"2026041123563879000_2025.03.18.643769v1.6","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/7316456"},{"key":"2026041123563879000_2025.03.18.643769v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/J.ISCI.2023.107915"},{"key":"2026041123563879000_2025.03.18.643769v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2012.05.007"},{"key":"2026041123563879000_2025.03.18.643769v1.9","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit937"},{"key":"2026041123563879000_2025.03.18.643769v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2018.12.011"},{"key":"2026041123563879000_2025.03.18.643769v1.11","doi-asserted-by":"crossref","unstructured":"Geretti, A.M. , Doyle, T .: Immunization for HIV-positive individuals. 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