{"doi":"10.1101/2022.01.19.476998","title":"Discovery of a SARS-CoV-2 Broadly-Acting Neutralizing Antibody with Activity against Omicron and Omicron + R346K Variants","abstract":"ABSTRACT The continual emergence of SARS-CoV-2 variants of concern, in particular the newly emerged Omicron (B.1.1.529) variant, has rendered ineffective a number of previously EUA approved SARS-CoV-2 neutralizing antibody therapies. Furthermore, even those approved antibodies with neutralizing activity against Omicron are reportedly ineffective against the subset of Omicron variants that contain a R346K substitution, demonstrating the continued need for discovery and characterization of candidate therapeutic antibodies with the breadth and potency of neutralizing activity required to treat newly diagnosed COVID-19 linked to recently emerged variants of concern. Following a campaign of antibody discovery based on the vaccination of Harbour H2L2 mice with defined SARS-CoV-2 spike domains, we have characterized the activity of a large collection of Spike-binding antibodies and identified a lead neutralizing human IgG1 LALA antibody, STI-9167. STI-9167 has potent, broad-spectrum neutralizing activity against the current SARS-COV-2 variants of concern and retained activity against the Omicron and Omicron + R346K variants in both pseudotype and live virus neutralization assays. Furthermore, STI-9167 nAb administered intranasally or intravenously provided protection against weight loss and reduced virus lung titers to levels below the limit of quantitation in Omicron-infected K18-hACE2 transgenic mice. With this established activity profile, a cGMP cell line has been developed and used to produce cGMP drug product intended for use in human clinical trials.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":297636,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9522,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":504619,"name":"Thomas Kraus","orcid":"0000-0001-9747-3776","position":1,"is_corresponding":false},{"id":897413,"name":"Heyue Zhou","orcid":"0000-0003-2456-1876","position":2,"is_corresponding":false},{"id":897414,"name":"Yanliang Zhang","orcid":"0000-0002-0460-2995","position":3,"is_corresponding":false},{"id":419670,"name":"Namir Shaabani","orcid":"0000-0003-3548-5899","position":4,"is_corresponding":false},{"id":559606,"name":"Soner Yildiz","orcid":"0000-0002-7235-6108","position":5,"is_corresponding":false},{"id":897415,"name":"Na Du","orcid":"0009-0006-0805-1680","position":6,"is_corresponding":false},{"id":416600,"name":"Alok Singh","orcid":"0000-0002-4959-3869","position":7,"is_corresponding":false},{"id":2411,"name":"Lisa Miorin","orcid":"0000-0003-0989-3178","position":8,"is_corresponding":false},{"id":985752,"name":"Donghui Li","orcid":"0000-0001-8466-8697","position":9,"is_corresponding":false},{"id":897998,"name":"Karen Stegman","orcid":null,"position":10,"is_corresponding":false},{"id":780116,"name":"Sabrina I. 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