Invasive Non-typhoidal Salmonella

Invasive non-typhoidal Salmonella (iNTS) is an invasive infection caused by two types of Salmonella bacteria, called Enteritidis and Typhimurium. It can lead to high fever, bloodstream infections, sepsis, and, in severe cases, death.

The World Health Organization identifies iNTS as a priority pathogen for research and development, including vaccines, due to its significant global health impact—with up to 500,000 cases leading to more than 79,000 deaths in 2019.

Most infections occur in infants and young children under five years of age in low- and middle-income countries in sub–Saharan Africa, where host risk factors for iNTS disease such as recent or current malaria, acute malnutrition, HIV infection, and moderate to severe anemia are common. Across all ages and settings there is a high case fatality ratio of approximately 14.5%.

The treatment of iNTS is complicated by emerging antibiotic resistance, which limits available therapeutic options. Many of the existing treatments are expensive or inaccessible to affected populations. Although several iNTS vaccines are under development, no licensed vaccine currently exists.

Developing an iNTS vaccine

Recognizing the urgent need for an iNTS vaccine, the International Vaccine Institute initiated a dedicated vaccine development program in 2018. This effort was significantly advanced in 2019 when the Wellcome Trust awarded a $3 million grant to IVI to support the identification and selection of promising iNTS vaccine candidates. It is a joint project between IVI and the World Health Organization. As part of this project, IVI is conducting a Full Value of Vaccine Assessment (FVVA) in collaboration with the World Health Organization, Shift Health, the London School of Hygiene & Tropical Medicine, New York University, and the Swiss Tropical and Public Health Institute. The FVVA evaluates the economic and public health impact of an iNTS vaccine to guide developers, manufacturers, investors, policymakers, and regulators strategies. Several meetings have been conducted to discuss these points with experts (Kigali, Geneva, Accra, Nairobi).

Since 2021, IVI has made significant strides in developing a bivalent iNTS (Salmonella Enteritidis and Salmonella Typhimurium) conjugate vaccine and a trivalent iNTS/typhoid conjugate vaccine in a large-scale manufacturing process. Key milestones include technology transfer to a contract manufacturing organization (CMO) and the successful completion of preclinical toxicology studies, confirming safety in animal models.

With the establishment of CMC (Chemistry, Manufacturing, and Controls) components, toxicity assessments, and stability data for the trivalent iNTS/typhoid vaccine, the project is now poised to transition from preclinical to clinical development.

Page updated: March 2025