Immunologic Responses to a Live Attenuated Oral Cholera Vaccine

The primary objective of this study is to evaluate the antibody response to the cholera vaccine, Vaxchora®, in healthy subjects.

Investigators also seek to evaluate additional markers of the adaptive immune response including plasmablasts, activated B cells, memory B cells, and T cell responses in healthy subjects receiving cholera vaccine, produce monoclonal antibodies against cholera, and evaluate the safety and reactogenicity in healthy subjects receiving cholera vaccine.

Study Overview

• Status: Completed
• Conditions: Cholera
• Intervention / Treatment: Drug: Vaxchora

Detailed Description

Vibrio cholerae causes an acute diarrheal disease responsible for more than 100,000 deaths and affects an estimated 3 to 5 million people annually. Recent epidemics in Haiti and Africa illustrate the continued reach of this pathogen. Across the globe, one billion people lack access to safe drinking water and are vulnerable to cholera. The increasing disease burden, and emergence of more virulent strains, suggest that more aggressive approaches to preventing cholera are needed. This includes renewed efforts to understand the mechanism of protective immunity against cholera and to improve the protective efficacy of current cholera vaccines.

Vaxchora is a live attenuated cholera vaccine that protects against some cholera strains. It has been approved by the FDA since June 2016. Since October, 2016, this vaccine has been recommended for certain travelers 18 through 64 years of age going to cholera-affected areas. The purpose of this study is to look at the immune responses to the FDA approved cholera vaccine (Vaxchora®).

This study aims to enroll 50 participants who will receive the Vaxchora live cholera vaccine, of whom 30 will undergo two procedures for small intestinal biopsies: one at screening and the other post vaccination (25 participants at Day 29 and 5 participants at day 90) by an upper endoscopy biopsy (EGD).

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30030
      • The Hope Clinic of Emory University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Capable of informed consent and provision of written informed consent before any study procedures
• Capable of attending all study visits according to the study schedule
• Are in good health, as determined by medical history and targeted physical exam related to this history
• Female subjects of childbearing age must have a negative urine pregnancy test before study vaccination, and must use two forms of contraception to avoid pregnancy within one month of Vaxchora administration

Exclusion Criteria:

• Have an acute illness within 72 hours before vaccination
• Have any acute or chronic medical condition that, in the opinion of the principal investigator, would make vaccination unsafe or interfere with the evaluation of immune response to study vaccination
• Have a suppressed immune system as a result of illness, immunosuppressive medication, chemotherapy, or radiation therapy within 3 years prior to study vaccination
• Have taken oral or parenteral corticosteroids of any dose within 30 days before study vaccination
• Reside with individuals under the age of 2 or with an immunocompromised individuals
• Have a known history of autoimmune disease
• Have a history of Guillain-Barre Syndrome
• Have plans to receive any vaccine from 28 days prior to study vaccination until Day 29
• Has previously received a cholera vaccine or have a known history of V. Cholerae.
• Have donated blood or blood products within 56 days before study vaccination, plan to donate blood at any time during the 56-day duration of subject study participation, or plan to donate blood within 56 days after the last blood draw
• Have known hypersensitivity or allergy to any component of the vaccine or history of anaphylaxis with a vaccine or vaccine component
• Have allergy to tetracycline and/or ciprofloxacin
• Are pregnant or breastfeeding or plan to within one month of vaccination
• Traveled to a cholera endemic area and had traveler's diarrhea in the previous 5 years
• Have abnormal stool pattern (fewer than 3 stools/ week or greater than 2 stools/ day) or regular use of laxatives in the last 6 months
• Have current or recent antibiotic use in the past 14 days
• Are healthcare workers who have direct contact with patients who are immunocompromised, have unstable medical conditions, or are under the age of 2
• Are childcare caregivers who have direct contact with children who are 2 years or younger
• Are employed in the food industry
• Have received any vaccine within the previous 21 days
• History of bleeding disorders or current use of warfarin, aspirin, heparin, nonsteroidal anti-inflammatory drugs (NSAIDs) or other blood thinner/ anticoagulant medications in the past week for subjects undergoing intestinal biopsies.
• Use of benzodiazepines or narcotics for subjects undergoing intestinal biopsies 4 weeks prior to the procedure
• Any contraindications to endoscopy/concerns of the anesthesiologist for subjects who agree for esophagogastroduodenoscopy (EGD)/biopsies
• Body mass index (BMI) > 35 kg/m^2
• Have a diagnosis of any small bowel disease. This includes but is not limited to inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, indeterminate colitis, or microscopic colitis), small bowel obstruction, celiac disease, h/o small bowel resection, small bowel lymphoma, Whipple's disease, primary intestinal lymphangiectasis, abdominal radiation.
• Current medications for the treatment of gastroesophageal reflux disease (GERD) or dyspepsia
• History of Helicobacter pylori (H. pylori) infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vaxchora Vaccination; Healthy participants will receive a single dose of oral live cholera vaccine.	Drug: Vaxchora; Vaxchora is a live attenuated cholera vaccine that provides immunity against V. cholerae serogroup O1. Participants will receive one single oral dose of 100 mL.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of Antibody Titers in Serum	Antibody response is evaluated as the level of antibody titers in serum. Higher vibriocidal antibody titers indicate greater protection against cholera.	Day 1 (pre-vaccination), Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasmablast Levels	Plasmablasts are collected via blood draw and isolated and assessed for counts by the study team.	Day 1 (pre-vaccination), Day 8, Day 29
Activated B Cell Levels	Activated B cells are collected via blood draw and isolated and assessed for counts by the study team.	Day 1 (pre-vaccination), Day 8, Day 29
Memory B Cell Levels	Memory B cells are collected via blood draw and isolated and assessed for counts by the study team. The level of memory B cells is evaluated as the percentage of antigen specific immunoglobulin (Ig) secreting cells divided by the total Ig secreting cells.	Day 1 (pre-vaccination), Day 29
Number of Monoclonal Antibodies Produced Per Participant	The number of antigen-specific monoclonal antibodies (mAbs) was assessed in a subset of participants on Day 8 post-vaccination. Peripheral blood mononuclear cells (PBMCs) were isolated, and antigen-specific plasmablasts were single-cell sorted using fluorescently labeled V. cholerae antigens (e.g., CTB and LPS). Paired immunoglobulin heavy and light chain variable regions were amplified by RT-PCR, cloned into expression vectors, and expressed in mammalian cells. The number of unique antigen-specific monoclonal antibodies was determined by binding assays (e.g., ELISA).	Day 8
Number of Cholera Toxin B (CTB) Specific Monoclonals and Lipopolysaccharide (LPS) Specific Monoclonal Antibodies Per Participant	The monoclonal antibodies obtained were characterized as cholera toxin B (CTB) specific monoclonals and lipopolysaccharide (LPS) specific monoclonals. The characterization of monoclonal antibodies against V. cholerae is assessed in a subset of participants.	Day 8
Number of Adverse Events	The number of solicited and unsolicited adverse events were collected.	Up to Day 8, Up to Day 29
Number of Serious Adverse Events	The number of serious adverse events were collected during the duration of the study.	Up to Day 365

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Nadine Rouphael, MD, Emory University

Publications and helpful links

General Publications

• Adekunle O, Dretler A, Kauffman RC, Cho A, Rouphael N, Wrammert J. Longitudinal analysis of human humoral responses after vaccination with a live attenuated V. cholerae vaccine. PLoS Negl Trop Dis. 2021 Sep 3;15(9):e0009743. doi: 10.1371/journal.pntd.0009743. eCollection 2021 Sep.

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2017
• Primary Completion (Actual): December 10, 2024
• Study Completion (Actual): November 6, 2025

Study Registration Dates

• First Submitted: August 14, 2017
• First Submitted That Met QC Criteria: August 14, 2017
• First Posted (Actual): August 16, 2017

Study Record Updates

• Last Update Posted (Actual): February 13, 2026
• Last Update Submitted That Met QC Criteria: February 11, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Vaccination; Infectious Diseases; Contagious Diseases; Tropical Medicine
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Vibrio Infections; Pathological Conditions, Signs and Symptoms; Communicable Diseases; Cholera; Vaxchora
• Other Study ID Numbers: IRB00097012; R01AI137127 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No