Cholera

Cholera is an acute diarrheal infection caused by ingestion of food or water contaminated with the bacterium Vibrio cholerae. It affects both children and adults and can kill within hours if not properly treated. The global burden of cholera is challenging to confirm because the majority of cases are not reported. Researchers estimate that approximately 1.3 billion people are at risk for cholera in endemic countries with an estimated 2.86 million cases occurring every year. Among these cases, a disproportionate number is among children between 1-5 years.

Cholera is a disease of poverty. It thrives in both rural and urban settings where overcrowding, poor sanitation, and limited access to safe water create ideal conditions for its spread. Rapid and deadly outbreaks can also occur following natural disasters and humanitarian crises when systems break down.

Improvements in water quality, hygiene, and sanitation have been recognized as essential measures in preventing and controlling cholera. While effective, these long-term measures are challenging to implement in countries with limited resources. Oral cholera vaccines (OCVs) can be an effective complementary tool that works in the short- to medium-term, especially during outbreaks when immediate action is needed.

Although a cholera vaccine (Dukoral) was developed for travelers to cholera-endemic areas, it was not priced affordably for regions with the highest disease burden.

Developing vaccines against cholera and putting them to use

The International Vaccine Institute’s Cholera Program focuses on accelerating the development and introduction of safe, effective, and affordable OCVs to combat epidemic and endemic cholera in low- and middle-income countries.

The OCVs that have supplied the global stockpile since its inception in 2013 were developed at IVI in partnership with Vabiotech (Viet Nam) and technology-transferred to Shantha Biotechnics (India) and EuBiologics (Republic of Korea) for large-scale production. The WHO pre-qualified these vaccines under the names Shanchol™ and Euvichol®/Euvichol-Plus®/Euvichol®-S, respectively.

IVI is working to increase OCV supply and advance cholera control in three ways:

1. Support to current manufacturers and technology transfers to new commercial partners to ensure adequate supply
2. Developing new next-generation cholera vaccines with improved characteristics
3. Supporting OCV use and introduction in endemic countries

“The cholera situation is dire, and the availability and use of oral cholera vaccine is an essential part of a multifaceted approach to cholera control and prevention, especially as outbreaks increase and the global vaccine supply remains strained.”

Dr. Julia Lynch, Director of IVI’s Cholera Program

Ensuring supply of OCV

In 2019, IVI partnered again with EuBiologics to simplify and reformulate OCV to lower the cost of production and increase production capacity. The immunogenicity of this simplified vaccine was demonstrated in a Phase III comparative clinical trial in Nepal in 2023. The following year, Euvichol®-S achieved WHO prequalification. The simplified formulation resulted in a 40% increase in production capacity over the existing Euvichol-Plus®. The availability of doses increased from 35 million to 45 million in 2024, and production capacity is expected to steadily grow.

In 2022, IVI initiated the technology transfer of the simplified formulation, OCV-S, to Biovac in South Africa, fulfilling a two-fold ambition to expand OCV production while demonstrating the capacity for end-to-end vaccine manufacturing in Africa. In 2024, IVI began a second technology transfer to India’s Biological E. Limited, equipping the company with the technical knowledge, expertise, and materials needed to produce OCV-S at its facilities.

Advancing new cholera vaccines

IVI is co-developing a cholera conjugate vaccine in collaboration with researchers at Massachusetts General Hospital, Harvard University. Conjugate vaccines elicit a durable T-cell-dependent immune response in young children, often with just a single dose. A cholera conjugate vaccine offers the potential for long-lasting protection including in young children and could be a cost-effective addition to the Expanded Programme on Immunization. The team completed a Phase I clinical trial in 2024 with plans to initiate the next phase in 2025.

Additionally, IVI is co-developing DuoChol, a novel OCV distinguished by its dry, capsule-based formulation. This format makes it more thermostable, lightweight, and efficient to store, transport, and distribute.

Supporting OCV use and introduction

The third objective in IVI’s Cholera Program is generating evidence to support the use of OCV in endemic countries. The Enhancing Cholera Control project in Nepal and the parallel project in Mozambique contribute to national cholera prevention and control while building up programs aligned with the Global Task Force on Cholera Control roadmap.

The project in Nepal focuses on strengthening diagnostic and surveillance capacity, enhancing rapid response to limit outbreaks, preventing cholera in hotspot regions through vaccinations, and fostering collaboration to develop an evidence-based cholera control plan.

During 2022-2024, the project in Mozambique made progress on disease surveillance activities and collecting data for a cost-of-illness study in endemic and outbreak areas. A cross-sectional population-based household survey was also carried out to better understand the health-seeking behavior of local populations and multifaceted risk factors related to cholera, including socio-economic and education status, and water, sanitation, and hygiene availability, access and utilization in households and communities in cholera-endemic setting.

The Ethiopia Cholera Control and Prevention (ECCP) project, one of IVI’s major vaccine delivery programs around the world, also aimed to support the Ethiopian government’s cholera control plan. In 2022, the project team conducted a preventive OCV mass vaccination campaign in one of the high-priority cholera hotspots, ultimately reaching a high vaccine coverage rate.

The team also established systematic cholera and diarrheal disease surveillance across multiple sentinel healthcare facilities, and a vaccine effectiveness study is ongoing. A strong research partnership between IVI, Armauer Hansen Research Institute (AHRI) and the Ethiopian Public Health Institute (EPHI) also enabled a comprehensive review of all OCV vaccinations carried out in Ethiopia during 2019-2023.

Further, the ECCP project played a critical role in the establishment of the AHRI-IVI Collaborating Center in Ethiopia in 2022, opening more opportunities for research and policy engagements on cholera and OCV uptake strategies.

Page updated: March 2025