{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:41:17Z","timestamp":1793385677956,"version":"4.5.0"},"posted":{"date-parts":[[2026,1,5]]},"group-title":"Microbiology","reference-count":10,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIH","award":["subcontract no. 0258-A700-4609 under federal contract no. 75N93021C00014"],"award-info":[{"award-number":["subcontract no. 0258-A700-4609 under federal contract no. 75N93021C00014"]}]},{"name":"NIH","award":["subcontract GR0010139-PO024016 under federal contract no. 75N93021C00016"],"award-info":[{"award-number":["subcontract GR0010139-PO024016 under federal contract no. 75N93021C00016"]}]},{"name":"NIH","award":["K08 AI180347"],"award-info":[{"award-number":["K08 AI180347"]}]},{"name":"NIH","award":["K24 AI155230"],"award-info":[{"award-number":["K24 AI155230"]}]},{"award":["INV019355"],"award-info":[{"award-number":["INV019355"]}],"id":[{"id":"https:\/\/ror.org\/0456r8d26","id-type":"ROR","asserted-by":"publisher"}]},{"award":["UR014016"],"award-info":[{"award-number":["UR014016"]}],"id":[{"id":"https:\/\/ror.org\/00hj8s172","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>As SARS-CoV-2 evolves, it evades existing immunity elicited by exposure to earlier strains of the virus. In response, vaccine manufacturers have updated COVID-19 vaccines annually since 2022, though immune imprinting to the ancestral strain has blunted antibody responses to modern viral variants. In early 2025, the JN.1 subvariant LP.8.1 was dominant and manufacturers updated mRNA vaccine formulations to target LP.8.1 (LP.8.1 MV). However, by late 2025, other subvariants were dominant (XFG and NB.1.8.1) or emerging (e.g., PE.1.4, BA.3.2, PY.1.1.1) around the world. It is critical to understand the extent to which updated vaccine boosters elicit titers against both their target strain and recent variants. Further, it is important to quantify the extent to which immune imprinting continues to shape antiviral immune responses. Using pseudoviruses, we measured neutralizing antibody titers against a panel of 11 SARS-CoV-2 variants in serum samples from 36 adult participants in the United States before and approximately 1 month after LP.8.1 MV booster. We found that neutralizing antibody titers were substantially increased by the boost, with the greatest increases elicited against LP.8.1 and XFG. For the first time since 2022, post-boost titers were higher against the homologous vaccine target (LP.8.1) than against D614G (representing the ancestral strain). Combined, these results indicate that ancestral immune imprinting is mitigated to the greatest extent observed to date by LP.8.1 MV. Lastly, for a subset of participants, we measured neutralizing titers at approximately 4 months post-booster and found that LP.8.1-directed antibody titers were durable, with an estimated average half-life of approximately 66 days.<\/jats:p>","DOI":"10.64898\/2026.01.03.697434","type":"posted-content","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T02:25:24Z","timestamp":1767666324000},"source":"Crossref","is-referenced-by-count":3,"title":["LP.8.1-directed COVID-19 mRNA vaccines durably boost neutralizing antibodies and mitigate ancestral immune imprinting"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6239-4821","authenticated-orcid":false,"given":"Ian A.","family":"Mellis","sequence":"first","affiliation":[{"name":"Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA"},{"name":"Department of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline","family":"Wu","sequence":"additional","affiliation":[{"name":"Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiang","family":"Hong","sequence":"additional","affiliation":[{"name":"Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA"},{"name":"Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1064-8372","authenticated-orcid":false,"given":"Anthony","family":"Bowen","sequence":"additional","affiliation":[{"name":"Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA"},{"name":"Division of Infectious Diseases, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Daniel","sequence":"additional","affiliation":[{"name":"Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA"},{"name":"Department of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Gherasim","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia M.","family":"Pierce","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Yin","sequence":"additional","affiliation":[{"name":"Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA"},{"name":"Division of Infectious Diseases, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9352-7877","authenticated-orcid":false,"given":"Aubree","family":"Gordon","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yicheng","family":"Guo","sequence":"additional","affiliation":[{"name":"Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David D.","family":"Ho","sequence":"additional","affiliation":[{"name":"Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA"},{"name":"Division of Infectious Diseases, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA"},{"name":"Pandemic Research Alliance unit at the Wu Center for Pandemic Research, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026031304500802000_2026.01.03.697434v2.1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmc2213907"},{"key":"2026031304500802000_2026.01.03.697434v2.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2024.01.014"},{"key":"2026031304500802000_2026.01.03.697434v2.3","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(25)00058-1"},{"key":"2026031304500802000_2026.01.03.697434v2.4","doi-asserted-by":"crossref","first-page":"116440","DOI":"10.1016\/j.celrep.2025.116440","article-title":"Antibody evasion and receptor binding of SARS-CoV-2 LP.8.1.1, NB.1.8.1, XFG, and related subvariants","volume":"44","year":"2025","journal-title":"Cell Rep"},{"key":"2026031304500802000_2026.01.03.697434v2.5","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/S1473-3099(25)00658-9","article-title":"Epidemiological and virological update on the emerging SARS-CoV-2 variant 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