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Here, we elucidated the longitudinal humoral immune repertoire over 3 years following prime and boost rVSV\u2206G-ZEBOV-GP vaccinations administered 18 months apart in healthy adults compared to participants randomized to no boost. This delayed booster vaccination induced long-lasting EBOV-neutralizing antibodies that persisted up to 36 month at levels similar to peak titers after a single dose. Phage display libraries, expressing linear and conformational epitopes of EBOV glycoprotein (GP), demonstrated a highly diverse and durable antibody epitope repertoire following prime boost vaccination. Delayed booster vaccination recalled memory B cells, promoted anti-GP IgG class switching and induced antibodies specific to GP with Fc\u03b3 receptor interaction and functional antibody-dependent cellular cytotoxicity and phagocytosis. The 18-month interval led to 13-fold higher antibody affinity maturation than a single dose, maintained up to 36 months. Overall, delayed rVSV\u2206G-ZEBOV-GP booster vaccination promoted a diverse, stronger, durable, predominant IgG, highly affinity-matured antibody response to GP.<\/jats:p>","DOI":"10.1038\/s41590-026-02459-w","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T10:03:15Z","timestamp":1773914595000},"page":"1053-1065","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Improved VSV-Ebola-GP booster vaccination approach promotes antibody affinity maturation and durable anti-Ebola immunity in humans"],"prefix":"10.1038","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0593-7965","authenticated-orcid":false,"given":"Surender","family":"Khurana","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Posadas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9135-6026","authenticated-orcid":false,"given":"Lela","family":"Kardava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"Coyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supriya","family":"Ravichandran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"Grubbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary","family":"McConnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2512-7919","authenticated-orcid":false,"given":"Nadine","family":"Rouphael","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Poliquin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3270-7345","authenticated-orcid":false,"given":"Joanne M.","family":"Langley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean A.","family":"Follmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3986-4557","authenticated-orcid":false,"given":"Xiaoran","family":"Shang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9785-2960","authenticated-orcid":false,"given":"Yuxing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0163-6911","authenticated-orcid":false,"given":"Susan","family":"Moir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Richard T.","family":"Davey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"2459_CR1","doi-asserted-by":"publisher","first-page":"20160292","DOI":"10.1098\/rstb.2016.0292","volume":"372","author":"CE Coltart","year":"2017","unstructured":"Coltart, C. 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