{"doi":"10.3389/fcimb.2023.1191806","title":"Monoclonal antibodies against lipopolysaccharide protect against Pseudomonas aeruginosa challenge in mice","abstract":"Pseudomonas aeruginosa is a common cause of hospital-acquired infections, including central line-associated bloodstream infections and ventilator-associated pneumonia. Unfortunately, effective control of these infections can be difficult, in part due to the prevalence of multi-drug resistant strains of P. aeruginosa . There remains a need for novel therapeutic interventions against P. aeruginosa , and the use of monoclonal antibodies (mAb) is a promising alternative strategy to current standard of care treatments such as antibiotics. To develop mAbs against P. aeruginosa , we utilized ammonium metavanadate, which induces cell envelope stress responses and upregulates polysaccharide expression. Mice were immunized with P. aeruginosa grown with ammonium metavanadate and we developed two IgG2b mAbs, WVDC-0357 and WVDC-0496, directed against the O-antigen lipopolysaccharide of P. aeruginosa . Functional assays revealed that WVDC-0357 and WVDC-0496 directly reduced the viability of P. aeruginosa and mediated bacterial agglutination. In a lethal sepsis model of infection, prophylactic treatment of mice with WVDC-0357 and WVDC-0496 at doses as low as 15 mg/kg conferred 100% survival against challenge. In both sepsis and acute pneumonia models of infection, treatment with WVDC-0357 and WVDC-0496 significantly reduced bacterial burden and inflammatory cytokine production post-challenge. Furthermore, histopathological examination of the lungs revealed that WVDC-0357 and WVDC-0496 reduced inflammatory cell infiltration. Overall, our results indicate that mAbs directed against lipopolysaccharide are a promising therapy for the treatment and prevention of P. aeruginosa infections.","journal":"Frontiers in Cellular and Infection Microbiology","year":2023,"id":341250,"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":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":943170,"name":"Margalida Mateu-Borrás","orcid":"0000-0002-6761-9663","position":1,"is_corresponding":false},{"id":1076749,"name":"Hunter L. Monroe","orcid":"0000-0003-4921-3827","position":2,"is_corresponding":false},{"id":399396,"name":"Emel Sen-Kilic","orcid":"0000-0003-1583-2056","position":3,"is_corresponding":false},{"id":15656,"name":"Sarah J. Miller","orcid":"0000-0003-4888-5306","position":4,"is_corresponding":false},{"id":1076750,"name":"Spencer R. Dublin","orcid":"0000-0001-6669-1519","position":5,"is_corresponding":false},{"id":501278,"name":"Annalisa B. Huckaby","orcid":"0000-0003-2044-1535","position":6,"is_corresponding":false},{"id":1077293,"name":"Evita Yang","orcid":null,"position":7,"is_corresponding":false},{"id":822207,"name":"Gage M. Pyles","orcid":"0000-0002-5782-5658","position":8,"is_corresponding":false},{"id":1053537,"name":"Mason A. Nunley","orcid":null,"position":9,"is_corresponding":false},{"id":1077294,"name":"Josh A. Chapman","orcid":null,"position":10,"is_corresponding":false},{"id":868845,"name":"Md Shahrier Amin","orcid":"0000-0003-3791-508X","position":11,"is_corresponding":false},{"id":399401,"name":"F. Heath Damron","orcid":"0000-0002-3140-402X","position":12,"is_corresponding":false},{"id":399402,"name":"Mariette Barbier","orcid":"0000-0002-3250-3636","position":13,"is_corresponding":false},{"id":745875,"name":"Jason Kang","orcid":"0000-0001-5736-0005","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T01:11:03.393978Z","pmid":"37424774","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":[]}