# Human B cell responses to a live attenuated cholera vaccine

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $390,000

## Abstract

PROJECT SUMMARY
 Vibrio cholerae causes an acute diarrheal disease that is estimated to lead to 3 to 5 million cases of
cholera and causes over 100,000 deaths annually. The increasing burden of cholera, the inability to achieve
benchmarks for sanitation and safe water, and the emergence of more virulent strains of V. cholerae suggest
that more aggressive approaches to preventing cholera, including vaccination programs, are needed.
However, currently available killed whole cell vaccines generate immunity that rapidly wanes and provides only
partial protection; especially in young children. In contrast, natural infection with V. cholerae induces 90-100 %
protection against re-infection that lasts for up to 10 years in adults and children. It remains unknown why
current vaccines are markedly less effective than natural infection. Understanding mucosal immunity and
mechanisms regulating homing of immune cells to mucosal tissues in humans is of key importance, not only
for V. cholerae infection, but for many other pathogens with a mucosal route of infection.
 A novel live attenuated cholera vaccine (Vaxchora) was recently approved in the US for use in
travelers. This vaccine has showed excellent protection in human challenge studies. However, little is known
about the long-term duration of protection, what determines the longevity of cholera specific memory B cells
and mucosal plasmacells, or what governs plasmacell migration to, and survival within, the intestinal mucosa.
In the current proposal, we seek to identify key differences in the early B cell responses after vaccination with
the live attenuated vaccine, that may predict long-term humoral immunity. We propose to draw upon existing
collaborations between the Emory Vaccine Center, the Emory Hope Clinic and the Massachusetts General
Hospital/Harvard Medical School (MGH/HMS) to address this question in humans. Specifically, we will study
both early and long term B cell responses in peripheral blood and in intestinal mucosae samples, using both
global and single cell approaches. These studies will provide unprecedented insight into heterogeneity of the
acute plasmablasts responses to cholera, their origin and activation process, affinity maturation and class
switching, mucosal homing potential, ability to provide long-lived immunity after infection is resolved, and the
antigenic specificity of the BCR, at a single cell level. Finally, imaging experiments will provide mechanistic
insight into the mode of action of anti-cholera antibodies. These studies will generate a large number of
monoclonal antibodies against cholera that might have both diagnostic and therapeutic uses. Findings herein
may also instruct future vaccine development for this important human pathogen.

## Key facts

- **NIH application ID:** 9950996
- **Project number:** 5R01AI137127-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Jens Peter Wrammert
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $390,000
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9950996

## Citation

> US National Institutes of Health, RePORTER application 9950996, Human B cell responses to a live attenuated cholera vaccine (5R01AI137127-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9950996. Licensed CC0.

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