Shigella Vaccine May Soon Stop Diarrheal Disease Outbreaks

Without much media attention, Shigellosis outbreaks have recently accelerated globally. Shigellosis has become a leading cause of fatal diarrheal disease worldwide, even in the United States. 

Shigellosis outbreaks cause up to 165 million infections due to Shigella, of which 62 million occur in children younger than five.

In the U.S., the Centers for Disease Control and Prevention (CDC) reported as of November 2, 2024, there have been 18,002 Shigella cases this year, led by California (3,864) and New York (2,647). 

However, the U.S. Food and Drug Administration (FDA) has not approved a Shigella vaccine, even though the World Health Organization (WHO) has identified it as a priority.

Based on today's announcement, a shigellosis vaccine candidate is proceeding to the approval finish line.

Valneva SE and LimmaTech Biologics AG announced today that the first participant had been vaccinated in a Phase 2b controlled human infection model (CHIM) study of Shigella4V2 (S4V2), the world's most clinically advanced tetravalent bioconjugate shigellosis vaccine candidate for which Valneva obtained an exclusive worldwide license from LimmaTech.

In the CHIM study S4V03, S4V2 will be tested for safety and preliminary efficacy in approximately 120 healthy Shigella-naïve participants aged 18 to 50 years at three sites in the U.S. 

The study, sponsored and conducted by LimmaTech, is a parallel-group, randomized, double-blind, multicenter, placebo-controlled study and will include two steps.

In the first step, the vaccine dose will be confirmed. In a second step, participants will be challenged with the Shigella sonnei strain 53G one month after injection of S4V2 or placebo to assess the ability of S4V2 to protect against the Shigella infection.

The infection rate of Shigellosis caused by the Shigella sonnei strain 53G in the group vaccinated with S4V2 will then be compared to that of the participants who received placebo injections.

Thomas Lingelbach, CEO of Valneva, commented, "Human challenge studies are unique in their ability to investigate and understand the onset and development of disease in a safe and highly controlled environment. This CHIM study forms part of our 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."

In addition to the CHIM study, LimmaTech will conduct a Phase 2 pediatric study in Low—and Middle-Income Countries, which is expected to begin before the end of 2024.

Valneva stated it will assume all further development, including chemistry, manufacturing, controls, and regulatory activities, and, if approved, be responsible for its commercialization worldwide.

Last month, the U.S. FDA granted the S4V2 Fast Track designation, recognizing its potential to address a serious condition and fill an unmet medical need.

The WHO says Shigellosis, a gastrointestinal infection caused by one of four species of Shigella bacteria, continues to pose a significant public health problem and remains endemic in many developing countries. Among Shigella species, Shigella dysenteriae type 1 (Sd1) represents a particular threat because of the severity of the disease it causes.