An anti-capsular antibody that cross protects against clade 1 Carbapenem-resistant Klebsiella pneumoniae

Therapeutic monoclonal antibodies (mAbs) have emerged as a dominant therapeutic modality to treat cancer, immune disorders, and infectious diseases such as high-mortality Carbapenem-resistant Klebsiella pneumoniae (CR-Kp). Although mAbs may combat the rising antibiotic resistance cases, antigenic diversity limits mAbs as a broader therapy- different strains often require different antibodies. There is an urgency to develop novel treatments to combat multidrug resistant pathogens; one of them being CR-Kp strain sequence type ST258, which is the most prevalent CR-Kp strain in the United States (60%). ST258 CR-Kp strains express different wzi types (wzi 50, 29, 154), however, so far only wzi154 strains have been successfully targeted by mAbs. Therefore, there is a specific need for a broader treatment method for CR-Kp strains that encompasses more of the wzi types.

Technology Overview:

The inventors have developed a murine mAb 24D11 (IgG2b isotype) by vaccinating mice with purified wzi50 type capsular polysaccharide (CPS). Cross-reactivity and protective efficacy of mAb 24D11 were confirmed against CR-Kp of 3 prevalent CPS types (wzi29, wzi154, and wzi50) using both in vitro and in vivo infection models. Using a murine intratracheal infection model, it has also been determined that mAb 24D11 reduced lung burden and dissemination of CR-Kp expressing different wzi-types, not only pre, but also if given 4 hours post infection. This is the first monoclonal antibody that exhibits cross-protective efficacy against multiple ST258 CR-Kp strains; it overcomes a major barrier to successfully target wzi29, a major CPS expressed by ST258 CR-Kp including that which caused the CR-Kp outbreak at the NIH in 2009.

Advantages:

Cross-reactivity and protective efficacy against multiple wzi CR-Kp - Antibody is effective pre and 4 hours post infection - Antibody reduced lung burden and dissemination of CR-Kp.

Applications:

Klebsiella infections

Intellectual Property Summary:

WO2023205731

Stage of Development:

Animal data

Licensing Status:

Available

Licensing Potential:

Development partner - Commercial partner - Licensing