Development of a Bispecific Antibody Targeting Clinical Isolates of Acinetobacter baumannii. (6th January 2023)

• Record Type: Journal Article
• Authors: Nielsen, Travis B; Yan, Jun; Slarve, Matthew; Li, Rachel; Junge, Jason A; Luna, Brian M; Wilkinson, Ian; Yerramalla, Udaya; Spellberg, Brad
• Is Part Of: Journal of infectious diseases. Volume 227:Number 9(2023)
• Page Start: 1042
• Page End: 1049
• Publication Date: 2023-01-06
• Subjects: Acinetobacter baumannii -- bispecific monoclonal antibody -- carbapenem resistant -- extreme drug resistance -- immunotherapy; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiac499
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Background: We previously reported developing 2 anticapsular monoclonal antibodies (mAbs) as a novel therapy for Acinetobacter baumannii infections. We sought to determine whether a bispecific mAb (bsAb) could improve avidity and efficacy while maximizing strain coverage in one molecule. Methods: Humanized mAb 65 was cloned into a single-chain variable fragment and attached to humanized mAb C8, combining their paratopes into a single bsAb (C73). We tested bsAb C73's strain coverage, binding affinity, ex vivo opsonic activity, and in vivo efficacy compared to each mAb alone and combined. Results: The bsAb demonstrated strain coverage, binding affinity, opsonization, and in vivo efficacy superior to either original mAb alone or combined. Conclusions: A humanized bsAb targeting distinct A. baumannii capsule moieties enabled potent and effective coverage of disparate A. baumannii clinical isolates. The bsAb enhances feasibility of development by minimizing the number of components of a promising novel therapeutic for these difficult-to-treat infections. Abstract : A bispecific antibody composed of 2 humanized monoclonal antibodies that target Acinetobacter baumannii demonstrated strain coverage, binding affinity, opsonization, and in vivo efficacy superior to either original monoclonal antibody alone or combined.