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Development of a Bispecific Antibody Targeting Clinical Isolates of Acinetobacter baumannii
- Source :
- The Journal of Infectious Diseases. 227:1042-1049
- Publication Year :
- 2023
- Publisher :
- Oxford University Press (OUP), 2023.
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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.
- Subjects :
- Infectious Diseases
Immunology and Allergy
Subjects
Details
- ISSN :
- 15376613 and 00221899
- Volume :
- 227
- Database :
- OpenAIRE
- Journal :
- The Journal of Infectious Diseases
- Accession number :
- edsair.doi.dedup.....5c0220a7f98b2e880dcd1fbcf2fb5baf