Valneva SE and LimmaTech Biologics have announced significant progress in their collaborative development of Shigella4V2 (S4V2), a tetravalent bioconjugate vaccine candidate targeting shigellosis, with the initiation of two critical Phase 2 clinical trials.
The companies reported that the first participant has been vaccinated in a Phase 2 infant safety and immunogenicity study in Kenya, targeting approximately 110 nine-month-old infants. This trial aims to identify the optimal dose for future Phase 3 testing. Concurrently, a Phase 2b controlled human infection model (CHIM) study is underway, involving approximately 120 healthy Shigella-naïve adults.
Shigellosis represents a significant global health challenge as the second leading cause of fatal diarrheal disease worldwide. The World Health Organization (WHO) estimates that up to 165 million Shigella infections occur annually, resulting in approximately 600,000 deaths, with children under five accounting for 62.3 million cases.
"Seeing so many infants and children dying from shigellosis is not acceptable if it can be prevented with a vaccine," said Dr. Juan Carlos, Chief Medical Officer of Valneva. "The development of Shigella vaccines has been identified as a priority by the World Health Organization."
Strategic Partnership Addresses Critical Vaccine Gap
The collaboration between Valneva and LimmaTech began in 2023 when Valneva paid €10 million upfront for rights to LimmaTech's vaccine candidate, previously developed in partnership with GSK. The agreement includes undisclosed regulatory, development, and sales-based milestone payments.
LimmaTech's S4V vaccine demonstrated promising results in Phase 1/2 trials, generating immune responses against the four most common pathogenic Shigella serotypes (S. flexneri 2a, 3a, 6, and S. sonnei) with a favorable safety profile.
Dr. Patricia Martin, Chief Operating Officer of LimmaTech, expressed optimism about the program: "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."
Urgent Need Amid Rising Antibiotic Resistance
The development of a Shigella vaccine has become increasingly urgent as antibiotic resistance continues to rise. Standard treatment for shigellosis involves oral rehydration and antibiotic therapy, but numerous outbreaks of multidrug-resistant strains have been reported, making treatment extremely challenging.
The U.S. Food and Drug Administration (FDA) has recognized this urgency by granting Fast Track designation to S4V2, acknowledging its potential to address a serious condition and fill an unmet medical need.
Development Strategy and Market Potential
The companies are employing a staggered and risk-mitigating development strategy. The infant study in Kenya, supported by funding from the Gates Foundation, is expected to yield results in the second half of 2025. Meanwhile, the CHIM study should provide the first efficacy results before potentially advancing to further studies.
According to Valneva, the global market for a Shigella vaccine could reach $500 million annually. Target populations include people in low- and middle-income countries, travelers, and military personnel deployed to regions where shigellosis is prevalent.
The WHO has established that an effective Shigella vaccine should demonstrate prevention of moderate to severe diarrhea with at least 60% efficacy and provide protection for a minimum of two years, preferably five.
Competitive Landscape
While S4V2 is described as the world's most clinically advanced tetravalent bioconjugate vaccine candidate against shigellosis, it is not alone in development. As of 2022, the WHO listed nine candidates in clinical trials, with a bivalent candidate from Beijing Zhifei Lvzhu Biopharmaceutical in Phase 3 testing.
For Valneva, this program adds to a growing portfolio that includes the world's first chikungunya vaccine (Ixchiq) and a Lyme disease vaccine candidate being developed in partnership with Pfizer.
If successful, S4V2 would be the first approved vaccine for shigellosis, potentially transforming the management of a disease that has been described as a "graveyard" for vaccine candidates despite decades of research.
