Vaccine- and Infection-derived Correlates of Protection for Cholera.
- Conditions
- Cholera
- Interventions
- Biological: oral cholera vaccine or typhoid conjugate vaccine
- Registration Number
- NCT06455852
- Lead Sponsor
- Massachusetts General Hospital
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1221
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cholera Vaccine Arm oral cholera vaccine or typhoid conjugate vaccine 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. Typhoid Vaccine Arm oral cholera vaccine or typhoid conjugate vaccine 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. Cholera Vaccine Arm oral cholera vaccine or typhoid conjugate vaccine We will measure mucosal, memory B cell and circulating antibody responses to V. cholerae in the participants using an established immunoprofiling approach. We will then identify individuals who develop V. cholerae infection over a two-year period, including those with mild and asymptomatic infection. We 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. Typhoid Vaccine Arm oral cholera vaccine or typhoid conjugate vaccine We 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.
- Primary Outcome Measures
Name Time Method Vibrio cholerae infection 2 years Serologic, PCR or culture evidence of infection
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Icddr,B
🇧🇩Dhaka, Bangladesh