# Active Vaccination and Passive Antibody Strategies to Prevent Klebsiella and Pseudomonas Disease

> **NIH NIH U19** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $543,161

## Abstract

Project summary – RP3
Klebsiella pneumoniae (KP) and Pseudomonas aeruginosa (PA) are major causes of healthcare-associated
Infections (HAI) including surgical site and wound infections, pneumonias, catheter based infections, urinary
tract infections, and septicemia, both in the USA and worldwide. Importantly, previously successful antibiotic
regimens for KP and PA are rapidly becoming ineffective due to the growing incidence of antimicrobial
resistance (AMR), including to antibiotics of last resort such as polymixin/colistin, threatening a return to the
pre-antibiotic era. As the clinico-epidemiological patterns for nosocomial infections with these pathogens are
similar, a broad spectrum approach is warranted and would offer a potentially straightforward way to
meaningfully reduce their combined incidence. Vaccine and prophylactic antibody approaches are unaffected
by the evasion mechanisms mediating resistance to antibiotics, and thus represent a promising approach
toward reducing the burden of AMR KP and PA infections. There are no available vaccines or antibody-based
preventive measures for KP and PA however. Our overall goal is to develop vaccine and antibody-based
countermeasures to prevent KP and PA HAIs. We propose here to continue assessment of a promising
glycoconjugate vaccine for KP and PA developed under Department of Defense funding that is based on
coupling of the four most common KP lipopolysaccharide-associated O polysaccharide (OPS) serotypes (60-
80% of clinical isolates worldwide) with the two types of PA flagellar major subunit proteins. We additionally
propose to develop a novel antibody-based approach to prevent KP colonization of the intestine, a major risk
factor for subsequent infection, by secretion of anti-KP fimbrial multi-specific single-chain antibody constructs
from an orally ingested Saccharomyces boulardii probiotic. In Aim 1, we will determine whether immunization
with the glycoconjugate generates immunity against relevant KP and PA clinical isolates in different challenge
models approximating pneumonia, sepsis and wound infection. In Aim 2, we will assess protection in models of
immunosenescence and immuno-compromise. Aims 3 and 4 will be focused on the development of a S.
boulardii strain engineered to secrete a multi-specific single-chain (VHH) antibody construct targeting the KP
fimbriae types important for intestinal attachment and colonization. These aims will assess whether conjugate
immunization and/or administration with S. boulardii secreting anti-fimbrial VHHs can prevent intestinal
colonization with KP. At the conclusion of this project, we expect to have generated important preclinical data
to support advancement of these products to Phase 1 clinical studies.

## Key facts

- **NIH application ID:** 9893805
- **Project number:** 5U19AI142725-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Raphael Simon
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $543,161
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893805

## Citation

> US National Institutes of Health, RePORTER application 9893805, Active Vaccination and Passive Antibody Strategies to Prevent Klebsiella and Pseudomonas Disease (5U19AI142725-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9893805. Licensed CC0.

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