# Optimization of therapeutic mAbs to carbapenem resistant Klebsiella clone ST258

> **NIH VA I01** · NORTHPORT VA MEDICAL CENTER · 2024 · —

## Abstract

Optimization of therapeutic mAbs to carbapenem resistant Klebsiella clones
Carbapenem resistant Klebsiella pneumoniae (CR-Kp) bacteria continue to be the most common gram-
negative multidrug-resistant bacteria in US hospitals. CR-Kp cause predominantly pneumonia, sepsis, and
urinary tract infections and, in military personnel, complicated invasive wound infections as well. Most
patients acquire this pathogen in health care-associated settings. Soldiers are at risk because they
commonly have prolonged stays in hospitals and rehabilitation centers when they recover from injuries they
sustained in combat. The mortality of invasive CR-Kp infections is high despite the introduction of novel
antibiotics. Monoclonal antibodies that bind to the capsule of CR-Kp are protective. One problem is that
most CR-Kp infections are diagnosed late and in patients with multiple comorbidities. One barrier to
generating monoclonal antibodies to the polysaccharide capsule is the heterogeneity of the polysaccharide
capsule. The goal of this application is to continue to optimize lead monoclonal antibodies (mAbs) that bind
to the diverse polysaccharide capsule (CPS) of CR-Kp. We now have a cross-protective monoclonal
antibody that binds to both clade 1 and clade 2 CR-Kp strains. Although the majority of CR-Kp strains belong
to the clonal group CG258 group, there is also another GC307 clone emerging, which expresses a
unique wzi173 capsule type. Based on others and our published experience we propose several strategies
to optimize mAb therapy to combat CR-Kp infections. Three aims are proposed. In Aim 1 we propose to
characterize in vitro and in vivo efficacy of humanized 24D11 (HU-24D11) which will be generated. In Aim
2 we will generate new mAbs that bind to the capsule (wzi173) of ST307. Finally, in Aim 3 we will explore
aerosilization as a novel delivery method to use CR-Kp-specific mAbs.
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## Key facts

- **NIH application ID:** 10802933
- **Project number:** 2I01BX003741-05A2
- **Recipient organization:** NORTHPORT VA MEDICAL CENTER
- **Principal Investigator:** Bettina Fries
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 2
- **Project period:** 2019-01-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10802933

## Citation

> US National Institutes of Health, RePORTER application 10802933, Optimization of therapeutic mAbs to carbapenem resistant Klebsiella clone ST258 (2I01BX003741-05A2). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10802933. Licensed CC0.

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