{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T07:38:36Z","timestamp":1774769916159,"version":"3.50.1"},"posted":{"date-parts":[[2024,12,17]]},"group-title":"Microbiology","reference-count":98,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T00:00:00Z","timestamp":1734393600000},"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":[[2024,12,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Rabies virus causes nearly 60,000 human deaths annually. Antibodies that target the rabies glycoprotein (G) are being developed as post-exposure prophylactics, but mutations in G can render such antibodies ineffective. Here, we use pseudovirus deep mutational scanning to measure how all single amino-acid mutations to G affect cell entry and neutralization by a panel of antibodies. These measurements identify sites critical for rabies G\u2019s function, and define constrained regions that are attractive epitopes for clinical antibodies, including at the apex and base of the protein. We provide complete maps of escape mutations for eight monoclonal antibodies, including some in clinical use or development. Escape mutations for most antibodies are present in some natural rabies strains. Overall, this work provides comprehensive information on the functional and antigenic effects of G mutations that can help inform development of stabilized vaccine antigens and antibodies that are resilient to rabies genetic variation.<\/jats:p>","DOI":"10.1101\/2024.12.17.628970","type":"posted-content","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T15:25:21Z","timestamp":1734708321000},"source":"Crossref","is-referenced-by-count":2,"title":["Deep mutational scanning of rabies glycoprotein defines mutational constraint and antibody-escape mutations"],"prefix":"10.64898","author":[{"given":"Arjun K.","family":"Aditham","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caelan E.","family":"Radford","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6912-6937","authenticated-orcid":false,"given":"Caleb R.","family":"Carr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naveen","family":"Jasti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil P.","family":"King","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1267-3408","authenticated-orcid":false,"given":"Jesse D.","family":"Bloom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024122311440953000_2024.12.17.628970v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)62707-5"},{"key":"2024122311440953000_2024.12.17.628970v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2014.07.004"},{"key":"2024122311440953000_2024.12.17.628970v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2018.11"},{"key":"2024122311440953000_2024.12.17.628970v1.4","doi-asserted-by":"publisher","DOI":"10.1080\/01652176.2017.1343516"},{"key":"2024122311440953000_2024.12.17.628970v1.5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003709"},{"key":"2024122311440953000_2024.12.17.628970v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2018.08.086"},{"key":"2024122311440953000_2024.12.17.628970v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijidoh.2023.100006"},{"key":"2024122311440953000_2024.12.17.628970v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2018.06.061"},{"key":"2024122311440953000_2024.12.17.628970v1.9","doi-asserted-by":"publisher","DOI":"10.4103\/jfmpc.jfmpc_890_20"},{"key":"2024122311440953000_2024.12.17.628970v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(18)30512-7"},{"key":"2024122311440953000_2024.12.17.628970v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39421-5"},{"key":"2024122311440953000_2024.12.17.628970v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2022.07.014"},{"key":"2024122311440953000_2024.12.17.628970v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2024.01.057"},{"key":"2024122311440953000_2024.12.17.628970v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2018.08.039"},{"key":"2024122311440953000_2024.12.17.628970v1.15","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines11040756"},{"key":"2024122311440953000_2024.12.17.628970v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2006.12.031"},{"key":"2024122311440953000_2024.12.17.628970v1.17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1186063"},{"key":"2024122311440953000_2024.12.17.628970v1.18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0006133"},{"key":"2024122311440953000_2024.12.17.628970v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2022.101204"},{"key":"2024122311440953000_2024.12.17.628970v1.20","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.9.7181-7190.1998"},{"key":"2024122311440953000_2024.12.17.628970v1.21","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.736114"},{"key":"2024122311440953000_2024.12.17.628970v1.22","doi-asserted-by":"publisher","DOI":"10.1002\/bip.360330612"},{"key":"2024122311440953000_2024.12.17.628970v1.23","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.150.3.601"},{"key":"2024122311440953000_2024.12.17.628970v1.24","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.65.9.4853-4859.1991"},{"key":"2024122311440953000_2024.12.17.628970v1.25","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abp9151"},{"key":"2024122311440953000_2024.12.17.628970v1.26","doi-asserted-by":"publisher","DOI":"10.1016\/J.CHOM.2019.12.012"},{"key":"2024122311440953000_2024.12.17.628970v1.27","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.67.3.1365-1372.1993"},{"key":"2024122311440953000_2024.12.17.628970v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2006.04.041"},{"key":"2024122311440953000_2024.12.17.628970v1.29","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-7-352"},{"key":"2024122311440953000_2024.12.17.628970v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/s0042-6822(03)00146-6"},{"key":"2024122311440953000_2024.12.17.628970v1.31","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2002.1429"},{"key":"2024122311440953000_2024.12.17.628970v1.32","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2022.2026713"},{"key":"2024122311440953000_2024.12.17.628970v1.33","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-13527-0"},{"key":"2024122311440953000_2024.12.17.628970v1.34","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201505986"},{"key":"2024122311440953000_2024.12.17.628970v1.35","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2019.1683436"},{"key":"2024122311440953000_2024.12.17.628970v1.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.02.001"},{"key":"2024122311440953000_2024.12.17.628970v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2023.05.025"},{"key":"2024122311440953000_2024.12.17.628970v1.38","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.549980"},{"key":"2024122311440953000_2024.12.17.628970v1.39","doi-asserted-by":"publisher","DOI":"10.3791\/56660"},{"key":"2024122311440953000_2024.12.17.628970v1.40","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1804015115"},{"key":"2024122311440953000_2024.12.17.628970v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108042"},{"key":"2024122311440953000_2024.12.17.628970v1.42","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd0826"},{"key":"2024122311440953000_2024.12.17.628970v1.43","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1707304114"},{"key":"2024122311440953000_2024.12.17.628970v1.44","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01962-14"},{"key":"2024122311440953000_2024.12.17.628970v1.45","doi-asserted-by":"publisher","DOI":"10.1093\/ve\/veac110"},{"key":"2024122311440953000_2024.12.17.628970v1.46","doi-asserted-by":"publisher","DOI":"10.2147\/ANTI.S33533"},{"key":"2024122311440953000_2024.12.17.628970v1.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2014.12.024"},{"key":"2024122311440953000_2024.12.17.628970v1.48","doi-asserted-by":"publisher","DOI":"10.3390\/tropicalmed2030048"},{"key":"2024122311440953000_2024.12.17.628970v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2008.08.050"},{"key":"2024122311440953000_2024.12.17.628970v1.50","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14398-7"},{"key":"2024122311440953000_2024.12.17.628970v1.51","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix791"},{"key":"2024122311440953000_2024.12.17.628970v1.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2024.05.066"},{"key":"2024122311440953000_2024.12.17.628970v1.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2021.08.066"},{"key":"2024122311440953000_2024.12.17.628970v1.54","unstructured":"Synermore Biologics (Suzhou) Co., Ltd. (2023). A Phase III Randomized Blinded Study to Evaluate SYN023 Compared to Human Rabies Immune Globulin in Post Exposure Prophylaxis of Rabies in Adults With Category III Rabies Exposure Risks (clinicaltrials.gov)."},{"key":"2024122311440953000_2024.12.17.628970v1.55","doi-asserted-by":"publisher","DOI":"10.1021\/bi980148j"},{"key":"2024122311440953000_2024.12.17.628970v1.56","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006271"},{"key":"2024122311440953000_2024.12.17.628970v1.57","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(92)90636-X"},{"key":"2024122311440953000_2024.12.17.628970v1.58","doi-asserted-by":"publisher","DOI":"10.1110\/ps.8.5.958"},{"key":"2024122311440953000_2024.12.17.628970v1.59","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2011.06.002"},{"key":"2024122311440953000_2024.12.17.628970v1.60","doi-asserted-by":"publisher","DOI":"10.4172\/jaa.1000061"},{"key":"2024122311440953000_2024.12.17.628970v1.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2024.10.002"},{"key":"2024122311440953000_2024.12.17.628970v1.62","doi-asserted-by":"publisher","DOI":"10.1002\/jmr.300030205"},{"key":"2024122311440953000_2024.12.17.628970v1.63","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2021.05.002"},{"key":"2024122311440953000_2024.12.17.628970v1.64","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1135(90)90156-P"},{"key":"2024122311440953000_2024.12.17.628970v1.65","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2012.03.044"},{"key":"2024122311440953000_2024.12.17.628970v1.66","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104122"},{"key":"2024122311440953000_2024.12.17.628970v1.67","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00787-10"},{"key":"2024122311440953000_2024.12.17.628970v1.68","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty407"},{"key":"2024122311440953000_2024.12.17.628970v1.69","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.50424"},{"key":"2024122311440953000_2024.12.17.628970v1.70","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34420"},{"key":"2024122311440953000_2024.12.17.628970v1.71","doi-asserted-by":"publisher","DOI":"10.1126\/science.abo7896"},{"key":"2024122311440953000_2024.12.17.628970v1.72","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-49487-4"},{"key":"2024122311440953000_2024.12.17.628970v1.73","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202012628"},{"key":"2024122311440953000_2024.12.17.628970v1.74","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PPAT.1007799"},{"key":"2024122311440953000_2024.12.17.628970v1.75","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2260"},{"key":"2024122311440953000_2024.12.17.628970v1.76","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004348"},{"key":"2024122311440953000_2024.12.17.628970v1.77","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4613-1755-5_2"},{"key":"2024122311440953000_2024.12.17.628970v1.78","doi-asserted-by":"publisher","DOI":"10.3390\/v13101989"},{"key":"2024122311440953000_2024.12.17.628970v1.79","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.047852-0"},{"key":"2024122311440953000_2024.12.17.628970v1.80","doi-asserted-by":"publisher","DOI":"10.1086\/500470"},{"key":"2024122311440953000_2024.12.17.628970v1.81","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.14.9062-9068.2005"},{"key":"2024122311440953000_2024.12.17.628970v1.82","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.8.4672-4678.2005"},{"key":"2024122311440953000_2024.12.17.628970v1.83","doi-asserted-by":"publisher","DOI":"10.21105\/joss.06129"},{"key":"2024122311440953000_2024.12.17.628970v1.84","unstructured":"Corti, D. (2016). Antibodies that potently neutralize rabies virus and other lyssaviruses and uses thereof."},{"key":"2024122311440953000_2024.12.17.628970v1.85","unstructured":"Bakker, A.B.H. , and Marissen, W.E. (2011). Liquid anti-rabies antibody formulations."},{"key":"2024122311440953000_2024.12.17.628970v1.86","unstructured":"Shen, E. , and Ren, S. (2013). Compositions and methods related to prevention and treatment of rabies infection."},{"key":"2024122311440953000_2024.12.17.628970v1.87","doi-asserted-by":"publisher","DOI":"10.1101\/2024.04.17.589977"},{"key":"2024122311440953000_2024.12.17.628970v1.88","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.06.013"},{"key":"2024122311440953000_2024.12.17.628970v1.89","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07636-1"},{"key":"2024122311440953000_2024.12.17.628970v1.90","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3002916"},{"key":"2024122311440953000_2024.12.17.628970v1.91","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2020.10.020"},{"key":"2024122311440953000_2024.12.17.628970v1.92","doi-asserted-by":"publisher","DOI":"10.1038\/387183a0"},{"key":"2024122311440953000_2024.12.17.628970v1.93","doi-asserted-by":"publisher","DOI":"10.1038\/343085a0"},{"key":"2024122311440953000_2024.12.17.628970v1.94","doi-asserted-by":"publisher","DOI":"10.1038\/71569"},{"key":"2024122311440953000_2024.12.17.628970v1.95","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00689-24"},{"key":"2024122311440953000_2024.12.17.628970v1.96","doi-asserted-by":"publisher","DOI":"10.21105\/joss.01915"},{"key":"2024122311440953000_2024.12.17.628970v1.97","doi-asserted-by":"publisher","DOI":"10.1101\/2023.07.31.551037"},{"key":"2024122311440953000_2024.12.17.628970v1.98","doi-asserted-by":"publisher","DOI":"10.21105\/joss.02906"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.12.17.628970","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T07:41:53Z","timestamp":1768462913000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.12.17.628970"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,17]]},"references-count":98,"URL":"https:\/\/doi.org\/10.1101\/2024.12.17.628970","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1016\/j.chom.2025.04.018","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2024,12,17]]},"subtype":"preprint"}}