Vaccine- and Infection-derived Correlates of Protection for Cholera

NCT06455852 | Recruiting DMC

• 1 other identifier: PR-24048
• Study Type: interventional
• Target: 1,221
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cholera

Outcome Measures

Primary Outcomes (1)

• Vibrio cholerae infection

  Serologic, PCR or culture evidence of infection

  2 years

Study Arms (2)

Cholera Vaccine Arm

EXPERIMENTAL

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

Typhoid Vaccine Arm

OTHER

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

Interventions

oral cholera vaccine or typhoid conjugate vaccine BIOLOGICAL

One group of participants will receive a 2 dose oral cholera vaccine, the other set will receive a typhoid conjugate vaccine

Cholera Vaccine Arm; Typhoid Vaccine Arm

Eligibility Criteria

• Age: 2 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.
• History of taking another oral cholera vaccine.
• History of taking any other live or killed enteric vaccine in the last 8 weeks.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• International Centre for Diarrhoeal Disease Research, Bangladesh: collaborator

Study Sites (1)

Icddr,B

Dhaka, Bangladesh

RECRUITING

MeSH Terms

Conditions

Cholera

Interventions

Cholera Vaccines

Condition Hierarchy (Ancestors)

Vibrio Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pediatrician

Study Record Dates

• First Submitted: June 7, 2024
• First Posted: June 12, 2024
• Study Start: March 2, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): May 1, 2029
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: Annually updated deidentified data will be provided and datasets will be provided with any study publication

Locations

BA (1)