# DEVELOPMENT OF A LIVE ORAL CHOLERA VACCINE

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 1993 · $291,365

## Abstract

DESCRIPTION:  (adapted from investigators abstract) The major long-term
objective of this project is the development of a live oral vaccine for the
prevention of cholera.  During the previous period of support, the
investigator and his coworkers developed candidate vaccine strains of
Vibrio cholerae using recombinant DNA techniques to delete portions of the
genes encoding cholera enterotoxin.  These strains provide strong
protection against challange when tested in volunteers but unexpectedly
caused diarrhea in many of them upon initial immunization.  In
investigating this phenomenon, a new secretogenic toxin in V. cholerae was
discovered; it is believed that this toxin is responsible for the observed
diarrhea.  This toxin affects the tight junctions, or zonula occludens,
which are found between epithelial cells.  The investigator hypothesizes
that this toxin causes diarrhea by the paracellular pathway rather than the
transcellular pathway which is affected by cholera enterotoxin.  Additional
studies have also resulted in several other new findings concerning
colonization and immunogenicity which serve as the basis for the propposed
future studies.

Specifically, Dr. Kaper proposes the following:  1) The new secretogenic
toxin (ZOT for zonula occludens toxin), will be characterized by purifying
it, raising specific antisera against it, and determining the human immune
response to it.  Using the zot gene which has already been cloned and
sequenced, the distribution and expression of ZOT in other strains will be
studied.  2) Attenuated V. cholerae vaccine strains of both classical and
El Tor biotypes which are mutated in genes encoding ZOT as well as in genes
encoding cholera toxin will be constructed.  3) The genetic defect in the
previously constructed vaccine candidate V. cholerae CVD103-HgR which is
responsible for decreased intestinal colonization of this strain relative
to the parent strain CVD103 will be characterized.  4) The investigator and
his coworkers will begin to study the genetic regulation of V. cholerae
antigens which are expressed in vivo but not in vitro and are immunogenic
in humans.  An expression library using a T7 promoter will be constructed
and screened with sera and jejunal fluid from convalescent patients to
detect genes encoding such antigens.  The genetic control of this
differential expression will be studied using gene fusions and proteins
expressed from cloned genes will be used to study the components of the
vibriocidal immune response.

## Key facts

- **NIH application ID:** 3129085
- **Project number:** 5R01AI019716-11
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **SAM.gov UEI:** Z9CRZKD42ZT1
- **Principal Investigator:** JAMES B KAPER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $291,365
- **Award type:** 5
- **Project period:** 1983-01-01 → 1995-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129085

## Citation

> US National Institutes of Health, RePORTER application 3129085, DEVELOPMENT OF A LIVE ORAL CHOLERA VACCINE (5R01AI019716-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129085. Licensed CC0.

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