# Vibrio cholerae intestinal colonization and vaccine development

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $518,377

## Abstract

Project Summary
Cholera is a severe dehydrating diarrheal disease caused by Vibrio cholerae, a Gram-negative rod that
colonizes the small intestine and produces cholera toxin, whose actions largely account for the symptoms of
cholera. Prevention of cholera through utilization of an effective vaccine could be of enormous benefit.
However, the currently available vaccine, Shancol, a killed whole cell preparation, has several limitations
including only modest efficacy, requirement for two doses, and a duration of activity that is likely less than that
engendered by natural infection with wild type V. cholerae. Live-attenuated vaccines offer the possibility of
overcoming these limitations, but the last live-attenuated vaccine for cholera that showed promise in human
trials was created more than 25 years ago and is no longer being developed. In the interim, the V. cholerae
strain causing cholera worldwide has evolved. A `variant' El Tor strain, the cause of the devastating and
ongoing cholera outbreak in Haiti, is now the predominant cause of cholera globally. During the current grant
period, we used the infant rabbit-based model of cholera we developed to create new approaches for
deepening our understanding of V. cholerae-host interactions during infection and created a new live-
attenuated vaccine, HaitiV, the first created in the variant El Tor V. cholerae background. Infant rabbits
orogastrically infected with HaitiV are colonized, but do not develop diarrhea, due to the absence of cholera
toxin and other diarrheagenic factors. Moreover, administration of HaitiV reduces subsequent intestinal
colonization by and diarrhea associated with wild type V. cholerae even prior to the development of adaptive
immunity. Killed HaitiV does not induce acute colonization resistance or protection from disease, suggesting
that killed vaccines (e.g. Shancol) would likewise lack this benefit. Studies to address HaitiV immunogenicity
are outside the scope of this proposal, but we anticipate, based on prior clinical studies of live vaccines, that
HaitiV will induce long-term immunity to cholera after a single dose. Rapid HaitiV vaccination-induced
colonization resistance also has great potential clinical impact and is amenable to study in infant rabbits. In
Aims 1 and 2 of this proposal, we will investigate how HaitiV antagonizes intestinal colonization by wild type V.
cholerae. In Aim 3, we will test whether we can augment HaitiV's capacity to prevent intestinal colonization and
disease caused by wild type V. cholerae. Collectively, these experiments will broaden our understanding of the
processes that govern V. cholerae intestinal colonization and colonization resistance. In addition, these studies
will potentially yield a transformative, multifunctional agent that will be effective both as a traditional vaccine,
inducing long term immunity, as well as for reactive vaccination for controlling the acute spread of epidemics
even before stimulation of an adaptive, lon...

## Key facts

- **NIH application ID:** 9944431
- **Project number:** 5R01AI042347-25
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Matthew K WALDOR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $518,377
- **Award type:** 5
- **Project period:** 1998-01-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9944431

## Citation

> US National Institutes of Health, RePORTER application 9944431, Vibrio cholerae intestinal colonization and vaccine development (5R01AI042347-25). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9944431. Licensed CC0.

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