Improving cholera vaccination impact through advances in gut mucosal immunology: outcomes of a 2025 expert consultation

A scientific consultation with experts in cholera immunology, vaccinology, and public health was convened in June 2025 to review the current understanding of gut mucosal immunology in relation to cholera and cholera vaccination and to identify critical knowledge gaps and urgent research needs. Areas for discussion included protective mechanisms, correlates of protection (CoPs), and strategies to enhance oral cholera vaccine (OCV) performance, especially in young children. Key recommendations included advancing immunological research, including standardization of mucosal immune response assays in humans, to better understand gut mucosal responses across age groups and to define improved CoPs. Modeling was highlighted as an essential tool to evaluate innovative strategies for optimizing the use of existing OCV targeted to specific contexts, e.g. alternative strategies in outbreaks; national/regional immunization days in endemic settings; and integration with other health interventions. Age-descending studies for evaluation of adjuvants (e.g. dmLT) to enhance cholera vaccine efficacy and durability, especially in children, were recommended, and under strict ethical control also the use of Controlled Human Infection Models (CHIMs) in cholera-endemic settings for evaluation of immune responses and vaccine candidates. The insights from the meeting provide a roadmap for both immediate and longer-term improvements in cholera vaccination impact and disease control.