# Preclinical evaluation of psoralen inactivation as a platform for developing a killed, whole cell vaccine for Enterotoxigenic E. coli (ETEC)

> **NIH NIH R03** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2020 · $77,500

## Abstract

Westcott.Project Summary/Abstract
Enterotoxigenic E. coli (ETEC), Shigella flexneri and Campylobacter jejuni are the predominant bacterial
causes of morbidity and mortality from gastrointestinal (GI) disease in the developing world. Episodes of acute
diarrhea caused by these agents have been linked to developmental defects and chronic GI syndromes.
Vaccines that are safe for use in young children as well as adult travelers and deployed military are needed to
prevent infection and post-infection sequellae caused by these organisms. Formalin inactivation is the current
standard for generating killed, whole cell bacterial vaccines. This approach does not require genetic
manipulations or extensive knowledge of antigens that induce protective immune responses. However,
formalin crosslinks proteins, which has the potential to destroy antigenic epitopes that induce protective
immune responses in the context of live bacterial infection. We propose to test the feasibility of an alternative
inactivation method to generate safe, whole cell vaccines for enteric bacteria. Psoralen is a photoactivatable
drug that reversibly intercalates into nucleic acids. Following irradiation with long wavelength UV light
(P+UVA), covalent inter-strand crosslinks form at pyrimidine residues, preventing genome replication. Since
P+UVA inactivates bacteria by crosslinking nucleic acids rather than proteins, we hypothesize that protein
antigens will be preserved in a native form, generating vaccines with superior immunogenicity. We have
successfully inactivated ETEC using P+UVA. With this proposal we will extend the ETEC work by comparing
P+UVA to formalin-inactivated ETEC with respect to antigen preservation and immunogenicity using
established in vitro assays and murine models. A direct comparative analysis of the 2 inactivation methods is
needed to assess the value and feasibility of the P+UVA approach as an agile platform for enteric bacterial
vaccines, and more generally for vaccines to prevent antibiotic-resistant bacterial infections that impact patient
care in hospital settings.
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## Key facts

- **NIH application ID:** 10042258
- **Project number:** 1R03AI153841-01
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Marlena Moors Westcott
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $77,500
- **Award type:** 1
- **Project period:** 2020-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10042258

## Citation

> US National Institutes of Health, RePORTER application 10042258, Preclinical evaluation of psoralen inactivation as a platform for developing a killed, whole cell vaccine for Enterotoxigenic E. coli (ETEC) (1R03AI153841-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10042258. Licensed CC0.

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