{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T09:28:12Z","timestamp":1775986092435,"version":"3.50.1"},"posted":{"date-parts":[[2024,7,16]]},"group-title":"Immunology","reference-count":63,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,7,16]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  The emergence of highly contagious and immune-evasive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has required reformulation of coronavirus disease 2019 (COVID-19) vaccines to target those new variants specifically. While previous infections and booster vaccinations can enhance variant neutralization, it is unclear whether the monovalent version, administered using either mRNA or protein-based vaccine platforms, can elicit\n                  <jats:italic>de novo<\/jats:italic>\n                  B-cell responses specific for Omicron XBB.1.5 variants. Here, we dissected the genetic antibody repertoire of 603 individual plasmablasts derived from five individuals who received a monovalent XBB.1.5 vaccination either with mRNA (Moderna or Pfizer\/BioNtech) or adjuvanted protein (Novavax). From these sequences, we expressed 100 human monoclonal antibodies and determined binding, affinity and protective potential against several SARS-CoV-2 variants, including JN.1. We then select two vaccine-induced XBB.1.5 mAbs, M2 and M39. M2 mAb was a\n                  <jats:italic>de novo,<\/jats:italic>\n                  antibody, i.e., specific for XBB.1.5 but not ancestral SARS-CoV-2. M39 bound and neutralized both XBB.1.5 and JN.1 strains. Our high-resolution cryo-electron microscopy (EM) structures of M2 and M39 in complex with the XBB.1.5 spike glycoprotein defined the epitopes engaged and revealed the molecular determinants for the mAbs\u2019 specificity. These data show, at the molecular level, that monovalent, variant-specific vaccines can elicit functional antibodies, and shed light on potential functional and genetic differences of mAbs induced by vaccinations with different vaccine platforms.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>GRAPHICAL ABSTRACT<\/jats:title>\n                  <jats:fig position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"602781v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.1101\/2024.07.15.602781","type":"posted-content","created":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T23:50:16Z","timestamp":1721173816000},"source":"Crossref","is-referenced-by-count":1,"title":["Dissecting human monoclonal antibody responses from mRNA- and protein-based XBB.1.5 COVID-19 monovalent vaccines"],"prefix":"10.64898","author":[{"given":"Raianna F.","family":"Fantin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordan J.","family":"Clark","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hallie","family":"Cohn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepika","family":"Jaiswal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bailey","family":"Bozarth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alesandro","family":"Civljak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vishal","family":"Rao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor","family":"Lobo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica R.","family":"Nardulli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Komal","family":"Srivastava","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy","family":"Yong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Andreata-Santos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaitlyn","family":"Bushfield","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward S.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gagandeep","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"PVI Study","family":"Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven H.","family":"Kleinstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Krammer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viviana","family":"Simon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Goran","family":"Bajic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila H.","family":"Coelho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024071812550430000_2024.07.15.602781v1.1","doi-asserted-by":"crossref","unstructured":"Y. Yang , L. Du , SARS-CoV-2 spike protein: a key target for eliciting persistent neutralizing antibodies., Signal Transduct. Target. Ther. 6, 95 (2021).","DOI":"10.1038\/s41392-021-00523-5"},{"key":"2024071812550430000_2024.07.15.602781v1.2","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/s41586-020-2548-6","article-title":"Potently neutralizing and protective human antibodies against SARS-CoV-2","volume":"584","year":"2020","journal-title":"Nature"},{"key":"2024071812550430000_2024.07.15.602781v1.3","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1038\/s41586-021-04386-2","article-title":"Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift","volume":"602","year":"2022","journal-title":"Nature"},{"key":"2024071812550430000_2024.07.15.602781v1.4","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/s41586-021-03720-y","article-title":"In vivo monoclonal antibody efficacy against SARS-CoV-2 variant strains","volume":"596","year":"2021","journal-title":"Nature"},{"key":"2024071812550430000_2024.07.15.602781v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06025-4"},{"key":"2024071812550430000_2024.07.15.602781v1.6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2220948120"},{"key":"2024071812550430000_2024.07.15.602781v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03807-6"},{"key":"2024071812550430000_2024.07.15.602781v1.8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2120976119"},{"key":"2024071812550430000_2024.07.15.602781v1.9","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2119451"},{"key":"2024071812550430000_2024.07.15.602781v1.10","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s41586-021-04385-3","article-title":"Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies","volume":"602","year":"2022","journal-title":"Nature"},{"key":"2024071812550430000_2024.07.15.602781v1.11","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/s41586-021-04387-1","article-title":"Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization","volume":"602","year":"2022","journal-title":"Nature"},{"key":"2024071812550430000_2024.07.15.602781v1.12","doi-asserted-by":"crossref","first-page":"104270","DOI":"10.1016\/j.ebiom.2022.104270","article-title":"SARS-CoV-2 Omicron BA.5: Evolving tropism and evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern","volume":"84","year":"2022","journal-title":"EBioMedicine"},{"key":"2024071812550430000_2024.07.15.602781v1.13","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/S0140-6736(21)02844-0","article-title":"Com-COV2 study group, Reduced neutralisation of SARS-CoV-2 omicron B.1.1.529 variant by post-immunisation serum","volume":"399","year":"2022","journal-title":"Lancet"},{"key":"2024071812550430000_2024.07.15.602781v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/d41586-021-03826-3"},{"key":"2024071812550430000_2024.07.15.602781v1.15","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.cell.2021.12.033","article-title":"mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant","volume":"185","year":"2022","journal-title":"Cell"},{"key":"2024071812550430000_2024.07.15.602781v1.16","doi-asserted-by":"crossref","unstructured":"P. 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Biol. 4, 874 (2021).","DOI":"10.1038\/s42003-021-02399-1"},{"key":"2024071812550430000_2024.07.15.602781v1.56","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/s41586-024-07215-4","article-title":"Automated model building and protein identification in cryo-EM maps","volume":"628","year":"2024","journal-title":"Nature"},{"key":"2024071812550430000_2024.07.15.602781v1.57","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910007493"},{"key":"2024071812550430000_2024.07.15.602781v1.58","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.3115"},{"key":"2024071812550430000_2024.07.15.602781v1.59","doi-asserted-by":"publisher","DOI":"10.1107\/s2059798319011471"},{"key":"2024071812550430000_2024.07.15.602781v1.60","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3330"},{"key":"2024071812550430000_2024.07.15.602781v1.61","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.01456"},{"key":"2024071812550430000_2024.07.15.602781v1.62","doi-asserted-by":"crossref","first-page":"e0247723","DOI":"10.1128\/mbio.02477-23","article-title":"An in vitro experimental pipeline to characterize the epitope of a SARS-CoV-2 neutralizing antibody","volume":"15","year":"2024","journal-title":"MBio"},{"key":"2024071812550430000_2024.07.15.602781v1.63","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.chom.2020.06.010","article-title":"Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike","volume":"28","year":"2020","journal-title":"Cell Host Microbe"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.07.15.602781","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T06:43:15Z","timestamp":1768459395000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.07.15.602781"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,16]]},"references-count":63,"URL":"https:\/\/doi.org\/10.1101\/2024.07.15.602781","relation":{},"subject":[],"published":{"date-parts":[[2024,7,16]]},"subtype":"preprint"}}