{"doi":"10.22203/ecm.v039a06","title":"Deriving a dose and regimen for anti-glucosaminidase antibody passive-immunisation for patients with Staphylococcus aureus osteomyelitis","abstract":"Staphylococcus aureus (S. aureus) osteomyelitis remains a major clinical problem. Anti-glucosaminidase (Gmd) antibodies (1C11) are efficacious in prophylactic and therapeutic murine models. Feasibility, safety and pharmacokinetics of 1C11 passive immunisation in sheep and endogenous anti-Gmd levels were quantified in osteomyelitis patients. 3 sheep received a 500 mg intravenous (i.v.) bolus of 1C11 and its levels in sera were determined by enzyme-linked immunosorbent assay (ELISA) over 52 d. A humanised anti-Gmd monoclonal antibody, made by grafting the antigen-binding fragment (Fab) portion of 1C11 onto the fragment crystallisable region (Fc) of human IgG1, was used to make a standard curve of mean fluorescent intensity versus concentration of anti-Gmd. Anti-Gmd serum levels were determined in 297 patients with culture-confirmed S. aureus osteomyelitis and 40 healthy controls. No complications or adverse events were associated with the sheep 1C11 i.v. infusion and the estimated circulating half-life of 1C11 was 23.7 d. Endogenous anti-Gmd antibody levels in sera of osteomyelitis patients ranged from < 1 ng/mL to 300 µg/mL, with a mean concentration of 21.7 µg/mL. The estimated circulating half-life of endogenous anti-Gmd antibodies in sera of 12 patients with cured osteomyelitis was 120.4 d. A clinically relevant administration of anti-Gmd (500 mg i.v. = 7 mg/kg/70 kg human) was safe in sheep. This dose was 8 times more than the endogenous anti-Gmd levels observed in osteomyelitis patients and was predicted to have a half-life of > 3 weeks. Anti-Gmd passive immunisation has potential to prevent and treat S. aureus osteomyelitis. Further clinical development is warranted.","journal":"European Cells and Materials","year":2020,"id":78468,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":410205,"name":"RD Southgate","orcid":null,"position":1,"is_corresponding":false},{"id":410206,"name":"Chunlei Jiao","orcid":null,"position":2,"is_corresponding":false},{"id":410207,"name":"E Gersz","orcid":null,"position":3,"is_corresponding":false},{"id":410208,"name":"JR Owen","orcid":null,"position":4,"is_corresponding":false},{"id":410209,"name":"SL Kates","orcid":null,"position":5,"is_corresponding":false},{"id":410210,"name":"CA Beck","orcid":null,"position":6,"is_corresponding":false},{"id":379250,"name":"Chao Xie","orcid":"0000-0001-6197-2506","position":7,"is_corresponding":false},{"id":410211,"name":"JL Daiss","orcid":null,"position":8,"is_corresponding":false},{"id":408551,"name":"Virginia Post","orcid":"0000-0003-4104-0044","position":9,"is_corresponding":false},{"id":408552,"name":"T. Fintan Moriarty","orcid":"0000-0003-2307-0397","position":10,"is_corresponding":false},{"id":388310,"name":"Stephan Zeiter","orcid":"0000-0002-8155-4202","position":11,"is_corresponding":false},{"id":410212,"name":"Schwarz Em","orcid":null,"position":12,"is_corresponding":false},{"id":379247,"name":"Gowrishankar Muthukrishnan","orcid":"0000-0001-7521-6154","position":13,"is_corresponding":false},{"id":410204,"name":"C C Lee","orcid":null,"position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-18T21:50:09.793321Z","pmid":"32003439","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}