Development of a Bispecific Antibody Targeting Clinical Isolates of Acinetobacter baumannii
TB Nielsen, J Yan, M Slarve, R Li… - The Journal of …, 2023 - academic.oup.com
The Journal of Infectious Diseases, 2023•academic.oup.com
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 …
(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 …
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.
Oxford University Press