# Active Vaccination and Passive Antibody Strategies to Prevent Disease Caused by Multidrug-Resistant Bacterial Pathogens

> **NIH NIH U19** · UNIVERSITY OF MARYLAND BALTIMORE · 2022 · $2,500,000

## Abstract

CETR OVERALL ABSTRACT
Widespread antimicrobial resistance (AMR), both in the USA and globally, has made it increasingly difficult to
treat enteric and invasive nosocomial bacterial infections that were previously responsive to antimicrobials.
Among the most important enteric bacterial pathogens that cause severe clinical disease and death if they
cannot be treated with effective antibiotics are ones that cause diarrhea, dysentery or enteric fever. Some
bacterial enteric pathogens are epidemiologically emerging or re-emerging, e.g.: multi-drug resistant H58
lineage of Salmonella Typhi; S. Paratyphi A; multi-drug resistant Shigella; drug-resistant Campylobacter jejuni
and Clostridium difficile. A few bacterial enteropathogens are of special interest from the civilian biodefense
perspective, as they have been used by nefarious individuals to promulgate bioterror (non-typhoidal
Salmonella [NTS]), or have properties that suit them to such a purpose (Shigella dysenteriae 1). Two of the
most important opportunistic drug-resistant bacterial pathogens that cause invasive infections in compromised
hosts are Klebsiella pneumoniae and Pseudomonas aeruginosa. Vaccines and other preventives against these
pathogens can ameliorate the AMR problem by preventing clinical disease, thereby precluding the need to
administer antibiotics and relieving selection pressure. The five projects described in this Center of Excellence
for Translational Research (CETR) proposal, bonded by the theme “Active Vaccination and Passive Antibody
Strategies to Prevent Disease Caused by Multidrug-Resistant Bacterial Pathogens”, will undertake translational
research towards developing the following countermeasures to prevent disease caused by important multi-drug
resistant bacterial pathogens: an improved Shigella live vector vaccine consisting of 6 attenuated strains of key
serotypes, each expressing protective antigens to prevent clinical illness caused by ETEC, as well as Shigella
(Project 1); engineered attenuated NTS strains representing serogroups B, C1, C2 & D to serve as a
multivalent broadly protective live oral vaccine (Project 2); a conjugate vaccine consisting of O polysaccharides
of K. pneumoniae serotypes O1, O2, O3 & O5, representing the vast majority of invasive isolates, linked to
flagellin type A or B of P. aeruginosa, to prevent invasive disease (Project 3); the probiotic yeast
Saccharomyces boulardii engineered to secrete antibodies against K. pneumoniae fimbriae that mediate
intestinal colonization, thereby diminishing a major risk factor (colonization) for invasive disease (Project 3);
recombinant S. boulardii that secrete antibodies directed against C. difficile toxins and somatic antigens or
against flagellin of C. jejuni, administered orally to inhibit gut colonization and prevent diarrheal disease
(Project 4); a compendium of immune response measurements to Salmonella serovars to identify correlates of
protection and guide development of broadly protective live ...

## Key facts

- **NIH application ID:** 10364708
- **Project number:** 5U19AI142725-04
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Myron Max Levine
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,500,000
- **Award type:** 5
- **Project period:** 2019-03-15 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10364708

## Citation

> US National Institutes of Health, RePORTER application 10364708, Active Vaccination and Passive Antibody Strategies to Prevent Disease Caused by Multidrug-Resistant Bacterial Pathogens (5U19AI142725-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10364708. Licensed CC0.

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