Patient-Derived Antibody Data Yields Development of Broadly Cross-Protective Monoclonal Antibody against ST258 Carbapenem-Resistant .

The most pressing challenge for the development of anti-capsular antibodies is maximizing coverage against the heterogenous capsular polysaccharide (CPS) of carbapenem-resistant Klebsiella pneumoniae (CR-). So far, only CR- with CPS has been successfully targeted by antibodies. Here, we present murine antibody 24D11, which was developed by vaccinating mice with purified -type CPS. Cross-reactivity and protective efficacy of MAb 24D11 were confirmed against CR- that express the 3 most prevalent CPS types (, , ) using both and infection models. 24D11 induced complement-mediated and independent opsonophagocytosis in macrophages as well as killing of all CR- strains in whole blood cells derived from healthy donors. In a murine intratracheal infection model, 24D11 reduced lung burden and dissemination of CR- strains when administered 4 h pre- or postinfection. The protective efficacy of 24D11 remained effective in neutropenic mice. This is the first antibody which exhibits cross-protective efficacy against clade 1 and 2 ST258 CR- strains. It overcomes a major barrier to successfully target , a major CPS expressed by ST258 CR-. The finding that 24D11 also exhibits potent protective efficacy against CR- strains highlights its high potential as a lead agent for the development of broadly active immunotherapy. Here, we present and data for the CPS-specific monoclonal antibody MAb 24D11, demonstrating its cross-protective efficacy against three prominent types (, , and ) of the carbapenem-resistant clonal group CG258. In a murine pulmonary infection model, MAb 24D11 reduced bacterial lung burden and dissemination to other organs even if administered 4 h postinfection. Its protective efficacy was also observed in neutropenic mice, which highlights its potential value in clinical settings where oncology patients with CG258 infections may also be neutropenic.