# Initial clinical evaluation of attenuated Shigella flexneri 2a live vector expressing enterotoxigenic Escherichia coli antigens, strain CVD 1208S-122.

> **NIH NIH U01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $1,391,457

## Abstract

Project Summary
Shigella and enterotoxigenic Escherichia coli (ETEC) represent two important enteric pathogens. There are no
vaccines to prevent both Shigella and ETEC. The Center for Vaccine Development's (CVD) mission to develop
vaccines that prevent diarrheal disease in the most vulnerable populations has resulted in construction of a
prototype Shigella-ETEC vaccine candidate strain, named CVD 1208S-122. Strain CVD 1208S-122 consists of
an attenuated ΔguaBA, Δset, Δsen Shigella flexneri 2a strain that has been engineered to express ETEC
colonization factor antigen I (CFA/I) and the B and A2 subunits of heat-labile enterotoxin (LThA2B) from genes
integrated into the Shigella chromosome. The overall goal of this proposal is to conduct a proof-of-concept,
randomized, double-blinded, placebo-controlled, dose-escalation Phase 1 clinical evaluation on a pilot cGMP
lot of strain CVD 1208S-122. Each dose of the live, attenuated vaccine will be administered in the inpatient
setting (Research Isolation Ward) and reactogenicity will be assessed over 96 hours (4 days) of direct
observation. Stool cultures will be performed, vaccine strains will be isolated from stool, and blood and stool
specimens will be analyzed for the immunologic responses to vaccination. This clinical trial is designed to be
narrowly focused to provide the preliminary assessment of safety, answer whether the strain is stable, and
evaluate the immunogenicity to our Shigella-ETEC combination vaccine approach.
Aim1. Assess the safety and tolerability of CVD 1208S-122.
Aim 2. Measure the excretion pattern, genetic stability, and transmissibility of CVD 1208S-122.
Aim 3. Examine the immune response to CVD 1208S-122.
These research aims will assessed within the context of a clinical trial to be conducted according to local legal
and regulatory requirements, applicable US federal regulations, ICH guidelines, and Good Clinical Practice
(GCP) standards. We have a plan for ensuring clinical monitoring, ongoing quality management with quality
assurance and quality control activities, external independent safety oversight, and data management.

## Key facts

- **NIH application ID:** 9848221
- **Project number:** 1U01AI143493-01A1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Eileen M. Barry
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,391,457
- **Award type:** 1
- **Project period:** 2020-07-07 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9848221

## Citation

> US National Institutes of Health, RePORTER application 9848221, Initial clinical evaluation of attenuated Shigella flexneri 2a live vector expressing enterotoxigenic Escherichia coli antigens, strain CVD 1208S-122. (1U01AI143493-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9848221. Licensed CC0.

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