{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T19:43:39Z","timestamp":1782935019787,"version":"3.54.5"},"posted":{"date-parts":[[2023,6,12]]},"group-title":"Immunology","reference-count":68,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,6,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  SARS-CoV-2 has the capacity to evolve mutations to escape vaccine-and infection-acquired immunity and antiviral drugs. A variant-agnostic therapeutic agent that protects against severe disease without putting selective pressure on the virus would thus be a valuable biomedical tool. Here, we challenged rhesus macaques with SARS-CoV-2 Delta and simultaneously treated them with aerosolized RBD-62, a protein developed through multiple rounds of\n                  <jats:italic>in vitro<\/jats:italic>\n                  evolution of SARS-CoV-2 RBD to acquire 1000-fold enhanced ACE2 binding affinity. RBD-62 treatment gave equivalent protection in upper and lower airways, a phenomenon not previously observed with clinically approved vaccines. Importantly, RBD-62 did not block the development of memory responses to Delta and did not elicit anti-drug immunity. These data provide proof-of-concept that RBD-62 can prevent severe disease from a highly virulent variant.\n                <\/jats:p>","DOI":"10.1101\/2023.06.09.544432","type":"posted-content","created":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T00:50:11Z","timestamp":1686617411000},"source":"Crossref","is-referenced-by-count":2,"title":["RBD-based high affinity ACE2 antagonist limits SARS-CoV-2 replication in upper and lower airways"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5526-6162","authenticated-orcid":false,"given":"Matthew","family":"Gagne","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara J.","family":"Flynn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher Cole","family":"Honeycutt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dillon R.","family":"Flebbe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shayne F.","family":"Andrew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha J.","family":"Provost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"McCormick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Van Ry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"McCarthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John-Paul M.","family":"Todd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saran","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Ting","family":"Teng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shir","family":"Marciano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinon","family":"Rudich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Pessaint","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Dodson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark G.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanne","family":"Andersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u0159\u00ed","family":"Zahradn\u00edk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha C.","family":"Nason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn E.","family":"Foulds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Kwong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Roederer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gideon","family":"Schreiber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Seder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.","family":"Douek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2023061508152500000_2023.06.09.544432v1.1","doi-asserted-by":"publisher","DOI":"10.1101\/2021.05.26.445838"},{"key":"2023061508152500000_2023.06.09.544432v1.2","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1016\/j.immuni.2021.06.003","article-title":"Analysis of SARS-CoV-2 variant mutations reveals neutralization escape mechanisms and the ability to use ACE2 receptors from additional species","volume":"54","year":"2021","journal-title":"Immunity"},{"key":"2023061508152500000_2023.06.09.544432v1.3","doi-asserted-by":"crossref","first-page":"100529","DOI":"10.1016\/j.xcrm.2022.100529","article-title":"mRNA-1273 and BNT162b2 mRNA vaccines have reduced neutralizing activity against the SARS-CoV-2 omicron variant","volume":"3","year":"2022","journal-title":"Cell Rep Med"},{"key":"2023061508152500000_2023.06.09.544432v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELL.2021.12.032"},{"key":"2023061508152500000_2023.06.09.544432v1.5","doi-asserted-by":"crossref","unstructured":"A. Muik et al., Neutralization of SARS-CoV-2 Omicron by BNT162b2 mRNA vaccine-elicited human sera. Science, eabn7591 (2022).","DOI":"10.1101\/2021.12.22.21268103"},{"key":"2023061508152500000_2023.06.09.544432v1.6","doi-asserted-by":"publisher","DOI":"10.1056\/nejmc2119641"},{"key":"2023061508152500000_2023.06.09.544432v1.7","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1056\/NEJMc2214293","article-title":"Neutralization against BA.2.75.2, BQ.1.1, and XBB from mRNA Bivalent Booster","volume":"388","year":"2023","journal-title":"N Engl J Med"},{"key":"2023061508152500000_2023.06.09.544432v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30895-3"},{"key":"2023061508152500000_2023.06.09.544432v1.9","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1056\/NEJMc2119270","article-title":"Effectiveness of BNT162b2 Vaccine against Omicron Variant in South Africa","volume":"386","year":"2022","journal-title":"N Engl J Med"},{"key":"2023061508152500000_2023.06.09.544432v1.10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2035389"},{"key":"2023061508152500000_2023.06.09.544432v1.11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2034577"},{"key":"2023061508152500000_2023.06.09.544432v1.12","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2021-069761"},{"key":"2023061508152500000_2023.06.09.544432v1.13","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2202542"},{"key":"2023061508152500000_2023.06.09.544432v1.14","doi-asserted-by":"crossref","first-page":"e2224657","DOI":"10.1001\/jamanetworkopen.2022.24657","article-title":"Association of Receiving a Fourth Dose of the BNT162b Vaccine With SARS-CoV-2 Infection Among Health Care Workers in Israel","volume":"5","year":"2022","journal-title":"JAMA Netw Open"},{"key":"2023061508152500000_2023.06.09.544432v1.15","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1056\/NEJMoa2201570","article-title":"Protection by a Fourth Dose of BNT162b2 against Omicron in Israel","volume":"386","year":"2022","journal-title":"N Engl J Med"},{"key":"2023061508152500000_2023.06.09.544432v1.16","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1016\/j.cell.2022.03.038","article-title":"mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits similar B cell expansion, neutralizing responses, and protection from Omicron","volume":"185","year":"2022","journal-title":"Cell"},{"key":"2023061508152500000_2023.06.09.544432v1.17","doi-asserted-by":"publisher","DOI":"10.1126\/science.adc9127"},{"key":"2023061508152500000_2023.06.09.544432v1.18","doi-asserted-by":"crossref","first-page":"104196","DOI":"10.1016\/j.ebiom.2022.104196","article-title":"Replicating RNA platform enables rapid response to the SARS-CoV-2 Omicron variant and elicits enhanced protection in naive hamsters compared to ancestral vaccine","volume":"83","year":"2022","journal-title":"EBioMedicine"},{"key":"2023061508152500000_2023.06.09.544432v1.19","doi-asserted-by":"crossref","first-page":"eabq2427","DOI":"10.1126\/sciimmunol.abq2427","article-title":"Omicron BA.1 breakthrough infection drives cross-variant neutralization and memory B cell formation against conserved epitopes","volume":"7","year":"2022","journal-title":"Sci Immunol"},{"key":"2023061508152500000_2023.06.09.544432v1.20","doi-asserted-by":"publisher","DOI":"10.1126\/science.abq1841"},{"key":"2023061508152500000_2023.06.09.544432v1.21","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/j.cell.2022.01.018","article-title":"Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination","volume":"185","year":"2022","journal-title":"Cell"},{"key":"2023061508152500000_2023.06.09.544432v1.22","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1056\/NEJMoa2116044","article-title":"Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients","volume":"386","year":"2022","journal-title":"N Engl J Med"},{"key":"2023061508152500000_2023.06.09.544432v1.23","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2118542"},{"key":"2023061508152500000_2023.06.09.544432v1.24","doi-asserted-by":"crossref","first-page":"757","DOI":"10.3947\/ic.2022.0123","article-title":"Nirmatrelvir\/Ritonavir Prescription Rate and Outcomes in Coronavirus Disease 2019: A Single Center Study","volume":"54","year":"2022","journal-title":"Infect Chemother"},{"key":"2023061508152500000_2023.06.09.544432v1.25","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm7148e2"},{"key":"2023061508152500000_2023.06.09.544432v1.26","doi-asserted-by":"crossref","first-page":"eadd7197","DOI":"10.1126\/sciadv.add7197","article-title":"Nirmatrelvir-resistant SARS-CoV-2 variants with high fitness in an infectious cell culture system","volume":"8","year":"2022","journal-title":"Sci Adv"},{"key":"2023061508152500000_2023.06.09.544432v1.27","doi-asserted-by":"crossref","unstructured":"S. Iketani et al., Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir. Nature, (2022).","DOI":"10.1101\/2022.08.07.499047"},{"key":"2023061508152500000_2023.06.09.544432v1.28","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.bbrc.2022.09.010","article-title":"Hotspot residues and resistance mutations in the nirmatrelvir-binding site of SARS-CoV-2 main protease: Design, identification, and correlation with globally circulating viral genomes","volume":"629","year":"2022","journal-title":"Biochem Biophys Res Commun"},{"key":"2023061508152500000_2023.06.09.544432v1.29","doi-asserted-by":"crossref","unstructured":"Y. Hu et al., Naturally occurring mutations of SARS-CoV-2 main protease confer drug resistance to nirmatrelvir. bioRxiv, 2022.2006.2028.497978 (2022).","DOI":"10.1101\/2022.06.28.497978"},{"key":"2023061508152500000_2023.06.09.544432v1.30","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1038\/s41564-021-00954-4","article-title":"SARS-CoV-2 variant prediction and antiviral drug design are enabled by RBD in vitro evolution","volume":"6","year":"2021","journal-title":"Nat Microbiol"},{"key":"2023061508152500000_2023.06.09.544432v1.31","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.1021\/acsbiomaterials.2c00419","article-title":"Gelatin Stabilizes Nebulized Proteins in Pulmonary Drug Delivery against COVID-19","volume":"8","year":"2022","journal-title":"ACS Biomater Sci Eng"},{"key":"2023061508152500000_2023.06.09.544432v1.32","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1126\/science.abl8912","article-title":"Protection against SARS-CoV-2 Beta variant in mRNA-1273 vaccine-boosted nonhuman primates","volume":"374","year":"2021","journal-title":"Science"},{"key":"2023061508152500000_2023.06.09.544432v1.33","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.cell.2021.12.002","article-title":"Protection from SARS-CoV-2 Delta one year after mRNA-1273 vaccination in rhesus macaques coincides with anamnestic antibody response in the lung","volume":"185","year":"2022","journal-title":"Cell"},{"key":"2023061508152500000_2023.06.09.544432v1.34","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/s41423-022-00838-5","article-title":"T cell epitopes in SARS-CoV-2 proteins are substantially conserved in the Omicron variant","volume":"19","year":"2022","journal-title":"Cell Mol Immunol"},{"key":"2023061508152500000_2023.06.09.544432v1.35","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0244-2"},{"key":"2023061508152500000_2023.06.09.544432v1.36","doi-asserted-by":"publisher","DOI":"10.1111\/IMR.13089"},{"key":"2023061508152500000_2023.06.09.544432v1.37","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.3389\/fimmu.2019.01787","article-title":"Remembrance of Things Past: Long-Term B Cell Memory After Infection and Vaccination","volume":"10","year":"2019","journal-title":"Front Immunol"},{"key":"2023061508152500000_2023.06.09.544432v1.38","unstructured":"R. R. Goel et al., Distinct antibody and memory B cell responses in SARS-CoV-2 naive and recovered individuals following mRNA vaccination. Sci Immunol 6, (2021)."},{"key":"2023061508152500000_2023.06.09.544432v1.39","doi-asserted-by":"crossref","unstructured":"M. I. Barton et al., Effects of common mutations in the SARS-CoV-2 Spike RBD and its ligand, the human ACE2 receptor on binding affinity and kinetics. Elife 10, (2021).","DOI":"10.7554\/eLife.70658"},{"key":"2023061508152500000_2023.06.09.544432v1.40","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.cell.2022.01.001","article-title":"Receptor binding and complex structures of human ACE2 to spike RBD from omicron and delta SARS-CoV-2","volume":"185","year":"2022","journal-title":"Cell"},{"key":"2023061508152500000_2023.06.09.544432v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(23)00051-8"},{"key":"2023061508152500000_2023.06.09.544432v1.42","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELL.2021.12.046"},{"key":"2023061508152500000_2023.06.09.544432v1.43","doi-asserted-by":"crossref","first-page":"104935","DOI":"10.1016\/j.isci.2022.104935","article-title":"Anti-human ACE2 antibody neutralizes and inhibits virus production of SARS-CoV-2 variants of concern","volume":"25","year":"2022","journal-title":"iScience"},{"key":"2023061508152500000_2023.06.09.544432v1.44","doi-asserted-by":"crossref","unstructured":"F. Zhang et al., Pan-sarbecovirus prophylaxis with human anti-ACE2 monoclonal antibodies. Nat Microbiol, (2023).","DOI":"10.1038\/s41564-023-01389-9"},{"key":"2023061508152500000_2023.06.09.544432v1.45","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc0870"},{"key":"2023061508152500000_2023.06.09.544432v1.46","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2014352117"},{"key":"2023061508152500000_2023.06.09.544432v1.47","doi-asserted-by":"crossref","first-page":"e12828","DOI":"10.15252\/emmm.202012828","article-title":"Humanized COVID-19 decoy antibody effectively blocks viral entry and prevents SARS-CoV-2 infection","volume":"13","year":"2021","journal-title":"EMBO Mol Med"},{"key":"2023061508152500000_2023.06.09.544432v1.48","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-89957-z"},{"key":"2023061508152500000_2023.06.09.544432v1.49","doi-asserted-by":"crossref","first-page":"e0068521","DOI":"10.1128\/JVI.00685-21","article-title":"Characterization of a Novel ACE2-Based Therapeutic with Enhanced Rather than Reduced Activity against SARS-CoV-2 Variants","volume":"95","year":"2021","journal-title":"J Virol"},{"key":"2023061508152500000_2023.06.09.544432v1.50","doi-asserted-by":"crossref","unstructured":"T. Capraz et al., Structure-guided glyco-engineering of ACE2 for improved potency as soluble SARS-CoV-2 decoy receptor. Elife 10, (2021).","DOI":"10.7554\/eLife.73641"},{"key":"2023061508152500000_2023.06.09.544432v1.51","doi-asserted-by":"crossref","first-page":"eabn7737","DOI":"10.1126\/scitranslmed.abn7737","article-title":"An engineered ACE2 decoy neutralizes the SARS-CoV-2 Omicron variant and confers protection against infection in vivo","volume":"14","year":"2022","journal-title":"Sci Transl Med"},{"key":"2023061508152500000_2023.06.09.544432v1.52","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1038\/s41598-023-27636-x","article-title":"Optimizing variant-specific therapeutic SARS-CoV-2 decoys using deep-learning-guided molecular dynamics simulations","volume":"13","year":"2023","journal-title":"Sci Rep"},{"key":"2023061508152500000_2023.06.09.544432v1.53","doi-asserted-by":"crossref","first-page":"106092","DOI":"10.1016\/j.isci.2023.106092","article-title":"Prophylaxis and treatment of SARS-CoV-2 infection by an ACE2 receptor decoy in a preclinical animal model","volume":"26","year":"2023","journal-title":"iScience"},{"key":"2023061508152500000_2023.06.09.544432v1.54","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-91809-9"},{"key":"2023061508152500000_2023.06.09.544432v1.55","doi-asserted-by":"crossref","first-page":"eabq6527","DOI":"10.1126\/sciadv.abq6527","article-title":"Optimized ACE2 decoys neutralize antibody-resistant SARS-CoV-2 variants through functional receptor mimicry and treat infection in vivo","volume":"8","year":"2022","journal-title":"Sci Adv"},{"key":"2023061508152500000_2023.06.09.544432v1.56","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1038\/s41586-022-05513-3","article-title":"Close relatives of MERS-CoV in bats use ACE2 as their functional receptors","volume":"612","year":"2022","journal-title":"Nature"},{"key":"2023061508152500000_2023.06.09.544432v1.57","doi-asserted-by":"crossref","unstructured":"V. Fumagalli et al., Nirmatrelvir treatment of SARS-CoV-2-infected mice blunts antiviral adaptive immune responses. EMBO Mol Med, e17580 (2023).","DOI":"10.15252\/emmm.202317580"},{"key":"2023061508152500000_2023.06.09.544432v1.58","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-01021-0"},{"key":"2023061508152500000_2023.06.09.544432v1.59","unstructured":"K. S. Corbett et al., Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. Science, eabj0299 (2021)."},{"key":"2023061508152500000_2023.06.09.544432v1.60","doi-asserted-by":"crossref","first-page":"106413","DOI":"10.1016\/j.isci.2023.106413","article-title":"Enhanced neutralization escape to therapeutic monoclonal antibodies by SARS-CoV-2 omicron sub-lineages","volume":"26","year":"2023","journal-title":"iScience"},{"key":"2023061508152500000_2023.06.09.544432v1.61","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36561-6"},{"key":"2023061508152500000_2023.06.09.544432v1.62","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/s41586-022-04594-4","article-title":"Antibody evasion properties of SARS-CoV-2 Omicron sublineages","volume":"604","year":"2022","journal-title":"Nature"},{"key":"2023061508152500000_2023.06.09.544432v1.63","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/S1473-3099(22)00733-2","article-title":"Omicron sublineage BQ.1.1 resistance to monoclonal antibodies","volume":"23","year":"2023","journal-title":"Lancet Infect Dis"},{"key":"2023061508152500000_2023.06.09.544432v1.64","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1056\/NEJMc2214302","article-title":"Efficacy of Antiviral Agents against Omicron Subvariants BQ.1.1 and XBB","volume":"388","year":"2023","journal-title":"N Engl J Med"},{"key":"2023061508152500000_2023.06.09.544432v1.65","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.immuni.2020.08.014","article-title":"A Potent Anti-Malarial Human Monoclonal Antibody Targets Circumsporozoite Protein Minor Repeats and Neutralizes Sporozoites in the Liver","volume":"53","year":"2020","journal-title":"Immunity"},{"key":"2023061508152500000_2023.06.09.544432v1.66","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1015536108"},{"key":"2023061508152500000_2023.06.09.544432v1.67","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1056\/NEJMoa2024671","article-title":"Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates","volume":"383","year":"2020","journal-title":"N Engl J Med"},{"key":"2023061508152500000_2023.06.09.544432v1.68","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.23670"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.06.09.544432","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T04:46:43Z","timestamp":1768452403000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.06.09.544432"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,12]]},"references-count":68,"URL":"https:\/\/doi.org\/10.1101\/2023.06.09.544432","relation":{},"subject":[],"published":{"date-parts":[[2023,6,12]]},"subtype":"preprint"}}