LimmaTech and Valneva: First shigellosis vaccination in Phase 2 infant study

Shigellosis is the second leading cause of fatal diarrheal disease worldwide, strongly contributing to pediatric morbidity and mortality. It is estimated that up to 165 million infections are due to Shigella of which 62.3 million occur in children younger than five years. Developing an effective vaccine to prevent this deadly disease is a public health imperative for many areas of the world.

In the Phase 2 study S4V02 (Identifier: NCT06523231), the safety and immunogenicity of S4V2 will be tested in approximately 110 nine-month-old infants with the goal of identifying the best dose to be tested in a Phase 3 trial. Sponsored and conducted by LimmaTech, S4V02 is a randomized, controlled, and blinded study conducted at a single study site in Kenya. Participants will receive a two-dose vaccination with one of two different vaccine dose levels of S4V2 or a control vaccine. Safety will be evaluated throughout the trial for approximately six months following the last vaccination. Results of the study, which is supported by funding from the Gates Foundation, are expected in the second half of 2025.

Dr. Juan Carlos, Chief Medical Officer of Valneva, commented, “Seeing so many infants and children dying from shigellosis is not acceptable if it can be prevented with a vaccine. As such, the development of Shigella vaccines has been identified as a priority by the World Health Organization (WHO) and, in line with our mission of developing vaccines against infectious diseases with unmet medical needs, we are focused on delivering a preventative solution against this deadly disease.”

Dr. Patricia Martin, Chief Operating Officer of LimmaTech, stated, “We are proud to be in a leading position in the development of a Shigella vaccine, and the initiation of this trial marks a significant milestone in our collaboration with Valneva to combat shigellosis. We are encouraged by the potential of S4V2 to provide a solution for a serious global health threat and make a profound impact in protecting the health of so many children worldwide.”

In November 2024, Valneva and LimmaTech announced vaccination of the first participant in a Phase 2b controlled human infection model (CHIM) study of S4V2 (Identifier: NCT06615375), in approximately 120 healthy Shigella-naïve participants aged 18 to 50 years. This CHIM study forms part of the companies’ staggered and risk-mitigating development strategy for S4V2, as it should provide the first results on efficacy before potentially advancing to further CHIM and Phase 3 studies.

The U.S. Food and Drug Administration (FDA) also granted Fast Track designation to S4V2, recognizing its potential to address a serious condition and fill an unmet medical need.

About Shigellosis
Shigellosis is a global health threat caused by the Gram-negative Shigella bacteria. It is estimated that up to 165 million infections are due to Shigella of which 62.3 million occur in children younger than five years. Diarrheal infection is one of the major causes of morbidity and mortality in numerous countries as well as in travelers and deployed military personnel in endemic regions. There are an estimated 600,000 deaths attributed to Shigella each year and it is the second leading cause for diarrheal deaths. The standard treatment for shigellosis is oral rehydration and antibiotic therapy, however, the bacteria have acquired resistance to many antibiotics with numerous reports of outbreaks of multidrug-resistant strains, making treatment extremely difficult. Currently, no licensed Shigella vaccine is available.