{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:54:53Z","timestamp":1782280493919,"version":"3.54.5"},"posted":{"date-parts":[[2025,10,2]]},"group-title":"Immunology","reference-count":68,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["5R37 AI037526"],"award-info":[{"award-number":["5R37 AI037526"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH Center for HIV\/AIDS Vaccine Immunology and Immunogen Discovery","award":["1UM1AI144462-01"],"award-info":[{"award-number":["1UM1AI144462-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Nanoparticle immunogens excel at rapidly inducing high levels of circulating antibodies and are being deployed as part of several novel vaccines. However, their ability to elicit memory B cell responses is less well understood. Here we compared serologic and memory B cell responses to prime boost vaccination with either SARS-CoV-2 Wuhan-Hu-1 mRNA vaccine, or protein nanoparticles: SARS-CoV-2 B.1.351 homotypic containing a single receptor binding domain (RBD); (homotypic beta) or a combination of different Sarbecovirus RBDs (mosaic 8b), respectively. The memory B cells elicited by the 3 vaccine regimens showed closely related antibody sequences, similar levels of somatic mutation and clonal diversity. The breadth of serologic responses elicited by the mosaic nanoparticles were comparable to the homotypic nanoparticle and superior to the mRNA vaccine for some mismatched strains. However, serum neutralizing titers to SARS-CoV-2 were highest after mRNA vaccination. The three vaccines elicited memory B cells that produced antibodies specific to a broad range of epitopes on the RBD that differed in a way that may reflect epitope masking. Monoclonal antibodies derived from memory B cells elicited by the mosaic 8b nanoparticle showed greater breadth against a panel of SARS-CoV-2 variants and SARS-CoV.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Significance Statement<\/jats:title>\n                  <jats:p>Nanoparticle vaccines are promising next-generation vaccine candidates, yet their capacity to generate durable memory B cell responses remains incompletely understood. We compared immune responses following SARS-CoV-2 mRNA, homotypic beta nanoparticle, or mosaic 8b nanoparticle vaccination in mice. Serum antibody neutralizing responses against a panel of SARS-CoV-2 variants elicited by an mRNA vaccine were equivalent or superior to those elicited by mosaic 8b nanoparticle vaccines. However, the monoclonal antibodies derived from memory B cells elicited by the mosaic 8b nanoparticle showed better neutralizing breadth against heterologous pseudoviruses. These findings highlight individual strengths of mRNA and nanoparticle vaccines and show that mosaic 8b nanoparticle immunogens can enhance the breadth of memory B cell-derived antibodies.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.10.01.679787","type":"posted-content","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T04:10:12Z","timestamp":1759464612000},"source":"Crossref","is-referenced-by-count":0,"title":["Memory B cell Development in Response to mRNA SARS-CoV-2 and Nanoparticle Immunization in Mice"],"prefix":"10.64898","author":[{"given":"Marie","family":"Wiatr","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Canis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna","family":"Hernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Gazumyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela S.","family":"Silva Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadman","family":"Shawraz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songhee","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Bieniasz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodora","family":"Hatziioannou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frauke","family":"Muecksch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel C.","family":"Nussenzweig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025100618050889000_2025.10.01.679787v1.1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061254"},{"key":"2025100618050889000_2025.10.01.679787v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1886"},{"key":"2025100618050889000_2025.10.01.679787v1.3","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12895"},{"key":"2025100618050889000_2025.10.01.679787v1.4","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.11.2996"},{"key":"2025100618050889000_2025.10.01.679787v1.5","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20161533"},{"key":"2025100618050889000_2025.10.01.679787v1.6","doi-asserted-by":"publisher","DOI":"10.1126\/science.adr6896"},{"key":"2025100618050889000_2025.10.01.679787v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2914"},{"key":"2025100618050889000_2025.10.01.679787v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.09.063"},{"key":"2025100618050889000_2025.10.01.679787v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-023-00897-3"},{"key":"2025100618050889000_2025.10.01.679787v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3460"},{"key":"2025100618050889000_2025.10.01.679787v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03696-9"},{"key":"2025100618050889000_2025.10.01.679787v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.04.003"},{"key":"2025100618050889000_2025.10.01.679787v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03207-w"},{"key":"2025100618050889000_2025.10.01.679787v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.01.050"},{"key":"2025100618050889000_2025.10.01.679787v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04527-1"},{"key":"2025100618050889000_2025.10.01.679787v1.16","doi-asserted-by":"crossref","unstructured":"Z. Wang et al., Humoral immunity to SARS-CoV-2 elicited by combination COVID-19 vaccination regimens. J Exp Med 219 (2022).","DOI":"10.1084\/jem.20220826"},{"key":"2025100618050889000_2025.10.01.679787v1.17","doi-asserted-by":"crossref","unstructured":"A. Cho et al., Antibody evolution to SARS-CoV-2 after single-dose Ad26.COV2.S vaccine in humans. J Exp Med 219 (2022).","DOI":"10.1084\/jem.20220732"},{"key":"2025100618050889000_2025.10.01.679787v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04060-7"},{"key":"2025100618050889000_2025.10.01.679787v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03324-6"},{"key":"2025100618050889000_2025.10.01.679787v1.20","doi-asserted-by":"publisher","DOI":"10.1126\/science.abn2688"},{"key":"2025100618050889000_2025.10.01.679787v1.21","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm7038e1"},{"key":"2025100618050889000_2025.10.01.679787v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(22)00345-0"},{"key":"2025100618050889000_2025.10.01.679787v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/S41586-022-04778-Y"},{"key":"2025100618050889000_2025.10.01.679787v1.24","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1016\/j.cell.2022.04.009","article-title":"Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine","volume":"185","year":"2022","journal-title":"Cell"},{"key":"2025100618050889000_2025.10.01.679787v1.25","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06025-4"},{"key":"2025100618050889000_2025.10.01.679787v1.26","doi-asserted-by":"publisher","DOI":"10.1126\/science.abm0829"},{"key":"2025100618050889000_2025.10.01.679787v1.27","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05609-w"},{"key":"2025100618050889000_2025.10.01.679787v1.28","doi-asserted-by":"crossref","first-page":"463","DOI":"10.15585\/mmwr.mm7217a3","article-title":"Effectiveness of Monovalent mRNA COVID-19 Vaccination in Preventing COVID-19-Associated Invasive Mechanical Ventilation and Death Among Immunocompetent Adults During the Omicron Variant Period - IVY Network, 19 U.S. States, February 1, 2022-January 31, 2023","volume":"72","year":"2023","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"2025100618050889000_2025.10.01.679787v1.29","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm7115e2"},{"key":"2025100618050889000_2025.10.01.679787v1.30","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2021-069761"},{"key":"2025100618050889000_2025.10.01.679787v1.31","doi-asserted-by":"publisher","DOI":"10.1126\/science.1118391"},{"key":"2025100618050889000_2025.10.01.679787v1.32","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-021-00652-2"},{"key":"2025100618050889000_2025.10.01.679787v1.33","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf6840"},{"key":"2025100618050889000_2025.10.01.679787v1.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.10.019"},{"key":"2025100618050889000_2025.10.01.679787v1.35","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2208425120"},{"key":"2025100618050889000_2025.10.01.679787v1.36","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12041"},{"key":"2025100618050889000_2025.10.01.679787v1.37","doi-asserted-by":"publisher","DOI":"10.1126\/science.1234150"},{"key":"2025100618050889000_2025.10.01.679787v1.38","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3927"},{"key":"2025100618050889000_2025.10.01.679787v1.39","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03365-x"},{"key":"2025100618050889000_2025.10.01.679787v1.40","doi-asserted-by":"publisher","DOI":"10.1038\/nature12202"},{"key":"2025100618050889000_2025.10.01.679787v1.41","doi-asserted-by":"publisher","DOI":"10.1126\/science.abq0839"},{"key":"2025100618050889000_2025.10.01.679787v1.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.04.024"},{"key":"2025100618050889000_2025.10.01.679787v1.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.07.052"},{"key":"2025100618050889000_2025.10.01.679787v1.44","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2501637122"},{"key":"2025100618050889000_2025.10.01.679787v1.45","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2622-0"},{"key":"2025100618050889000_2025.10.01.679787v1.46","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-023-01389-9"},{"key":"2025100618050889000_2025.10.01.679787v1.47","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00650-10"},{"key":"2025100618050889000_2025.10.01.679787v1.48","doi-asserted-by":"publisher","DOI":"10.3201\/eid1906.121648"},{"key":"2025100618050889000_2025.10.01.679787v1.49","doi-asserted-by":"publisher","DOI":"10.1101\/2021.05.26.445838"},{"key":"2025100618050889000_2025.10.01.679787v1.50","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04005-0"},{"key":"2025100618050889000_2025.10.01.679787v1.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.12.004"},{"key":"2025100618050889000_2025.10.01.679787v1.52","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0244-2"},{"key":"2025100618050889000_2025.10.01.679787v1.53","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2852-1"},{"key":"2025100618050889000_2025.10.01.679787v1.54","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd2321"},{"key":"2025100618050889000_2025.10.01.679787v1.55","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2456-9"},{"key":"2025100618050889000_2025.10.01.679787v1.56","doi-asserted-by":"crossref","unstructured":"Z. Wang et al., Memory B cell development elicited by mRNA booster vaccinations in the elderly. J Exp Med 220 (2023).","DOI":"10.1084\/jem.20230668"},{"key":"2025100618050889000_2025.10.01.679787v1.57","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.vaccine.2016.12.049","article-title":"Nanoparticles decorated with viral antigens are more immunogenic at low surface density","volume":"35","year":"2017","journal-title":"Vaccine"},{"key":"2025100618050889000_2025.10.01.679787v1.58","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-065X.2003.00058.x"},{"key":"2025100618050889000_2025.10.01.679787v1.59","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.13.040195.003255"},{"key":"2025100618050889000_2025.10.01.679787v1.60","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.23.3.284-a"},{"key":"2025100618050889000_2025.10.01.679787v1.61","doi-asserted-by":"crossref","unstructured":"C. Viant et al., Germinal center-dependent and -independent memory B cells produced throughout the immune response. J Exp Med 218 (2021).","DOI":"10.1084\/jem.20202489"},{"key":"2025100618050889000_2025.10.01.679787v1.62","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03738-2"},{"key":"2025100618050889000_2025.10.01.679787v1.63","doi-asserted-by":"crossref","unstructured":"F. Schmidt et al., Measuring SARS-CoV-2 neutralizing antibody activity using pseudotyped and chimeric viruses. J Exp Med 217 (2020).","DOI":"10.1084\/jem.20201181"},{"key":"2025100618050889000_2025.10.01.679787v1.64","doi-asserted-by":"publisher","DOI":"10.1056\/nejmc2119641"},{"key":"2025100618050889000_2025.10.01.679787v1.65","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abf1555"},{"key":"2025100618050889000_2025.10.01.679787v1.66","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv359"},{"key":"2025100618050889000_2025.10.01.679787v1.67","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0934-8"},{"key":"2025100618050889000_2025.10.01.679787v1.68","doi-asserted-by":"crossref","unstructured":"Y. Guo , K. Chen , P. D. Kwong , L. Shapiro , Z. Sheng , cAb-Rep: a database of curated antibody repertoires for exploring antibody diversity and predicting antibody prevalence. Frontiers in immunology, 2365 (2019).","DOI":"10.1101\/765099"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.10.01.679787","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:03:03Z","timestamp":1782277383000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.10.01.679787"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,2]]},"references-count":68,"URL":"https:\/\/doi.org\/10.1101\/2025.10.01.679787","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1073\/pnas.2527869123","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,10,2]]},"subtype":"preprint"}}