Vaccine- and Infection-derived Correlates of Protection for Cholera (CoP)

Background: Vibrio cholerae causes millions of cholera cases and thousands of deaths annually. Vaccines are in short supply. There is no agreement on how to introduce new vaccines or evaluate their effectiveness, and the lack of 'correlates of protection' (CoPs) against cholera is a major obstacle to vaccine development. CoPs are markers of effective immune response to vaccination. While other infectious diseases have well established CoPs, none are widely accepted for cholera.

Relevance: Lack of accepted CoPs impedes development of cholera vaccines, limiting progress toward improved vaccines, slowing the licensure of new vaccines, and contributing to the current vaccine shortage; an immediate obstacle to achieving reductions in cholera-related illness and deaths. The identification of new CoPs will speed the development of improved cholera vaccines and provide a pathway to their licensure and use.

Hypothesis: The investigators hypothesize that some individuals who receive inactivated oral cholera vaccine (OCV) will develop antibody responses which predict protection against V. cholerae infection and that specific immune responses distinguish individuals who are protected against cholera by prior natural infection from those who are protected from OCVs.

Objectives: The investigators will administer an OCV or typhoid vaccine (TCV) control and monitor antibody responses to identify better CoPs for cholera following both vaccination and natural infection.

Methods: The investigators will randomize 1219 participants; 554 participants will receive an inactivated bivalent OCV, 665 participants will receive a TCV control. The investigators will collect 12 blood samples over two-years following vaccination to measure antibodies against V. cholerae and to monitor for re-infection.

Outcome measures/variables: The endpoint of interest is V. cholerae infection after vaccination. The investigators define infection as positive culture or PCR for V. cholerae or seroconversion events observed over the 2-year follow up period.

Study Overview

• Status: Recruiting
• Conditions: Cholera
• Intervention / Treatment: Biological: oral cholera vaccine or typhoid conjugate vaccine

• Study Type: Interventional
• Enrollment (Estimated): 1221
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Bangladesh
  • Dhaka, Bangladesh
    • Recruiting
    • Icddr,b
    • Contact: Firduasi Qadri, Ph.D.; Phone Number: 88-01711595367; Email: fqadri@icddrb.org
    • Principal Investigator: Firdausi Qadri, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria

1. Ages 2 - 80 years.
2. Informed consent from study participants and guardian in case of children (2-17 years) and assent from children aged 11-17 years.
3. Intention to participate in the study for a 2-year period.
4. No major co-morbid conditions, per the supervising clinician investigator, including underlying immunodeficiency, diabetes, liver diseases, renal disease, cardiac disease, and/or active malignancy.

Exclusion criteria

1. Suffering from diarrhoea or abdominal pain or vomiting in the past 24 hours or diarrhoea lasting for more than 2 weeks in the past 6 months.
2. History of taking another oral cholera vaccine.
3. History of taking any other live or killed enteric vaccine in the last 8 weeks.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cholera Vaccine Arm; The investigators will measure mucosal, memory B cell and circulating antibody responses to V. cholerae in the participants using an established immunoprofiling approach. The investigators will then identify individuals who develop V. cholerae infection over a two-year period, including those with mild and asymptomatic infection. They will use a systems-serology approach to identify CoPs in the OCV (bWC) cohort and non-OCV vaccinated control (TCV) cohort. Our approach will include cross-validation and adjustments for age, sex, and baseline immunity, to identify vaccine-induced CoPs. We will also compare the performance of these CoPs with the traditional vibriocidal titer.	Biological: oral cholera vaccine or typhoid conjugate vaccine; One group of participants will receive a 2 dose oral cholera vaccine, the other set will receive a typhoid conjugate vaccine
Other: Typhoid Vaccine Arm; The investigators will compare individual CoPs and immunologic signatures in the OCV and non-cholera vaccinated (TCV) control arms which are correlated with protection. This will identify individual CoPs and immunologic signatures which distinguish protective immunity derived from natural infection with V. cholerae from immunity derived from inactivated OCV response.	Biological: oral cholera vaccine or typhoid conjugate vaccine; One group of participants will receive a 2 dose oral cholera vaccine, the other set will receive a typhoid conjugate vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vibrio cholerae infection	Serologic, PCR or culture evidence of infection	2 years

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: International Centre for Diarrhoeal Disease Research, Bangladesh

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: June 7, 2024
• First Submitted That Met QC Criteria: June 7, 2024
• First Posted (Actual): June 12, 2024

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Vibrio Infections; Cholera; Biological Products; Complex Mixtures; Bacterial Vaccines; Vaccines; Cholera Vaccines
• Other Study ID Numbers: PR-24048

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: A data sharing plan will be developed in accordance with funder regulations and institutional policies. Deidentified data will be shared upon publication of study results.
• IPD Sharing Time Frame: Annually updated deidentified data will be provided and datasets will be provided with any study publication
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No