Valneva reports positive Phase 2 results for Shigella vaccine candidate S4V2

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Valneva said on Monday that its experimental Shigella vaccine S4V2 produced positive results in two Phase 2 trials, one in infants in Kenya and one in healthy adults deliberately exposed to the bacterium in the United States. The French vaccine maker called S4V2 the most clinically advanced tetravalent vaccine candidate against shigellosis, a diarrhoeal disease for which no vaccine is licensed.

In the infant trial, 110 nine-month-old babies in Kenya received two doses of S4V2 or a control meningococcal vaccine. The vaccine was well tolerated at both dose levels, with most side effects mild to moderate and no statistical difference from the control group, and every treatment-related side effect resolved without complications. After the two-dose course, antibody levels against all four targeted Shigella serotypes rose significantly compared with the control group, peaking after the second dose and staying above baseline six months later.

The second trial, a controlled human infection study in about 120 healthy adults aged 18 to 50 at three sites in the United States, gave participants two doses of S4V2 or placebo a month apart, then exposed them to the Shigella sonnei 53G strain about a month after the second dose. The trial met its primary endpoint: those who received the vaccine developed shigellosis caused by S. sonnei significantly less often than those given placebo.

Valneva's own announcement is the source for every figure in this report, and it leaves some important questions unanswered. The release gives no size for the reduction in shigellosis in the infection trial and no numerical antibody levels from the infant trial, so the scale of the benefit cannot be judged from what has been published so far. The full datasets have not yet appeared in a peer-reviewed journal, and Valneva says further analysis of efficacy and immune responses is still under way. LimmaTech sponsored both trials, and the infant trial was funded by the Gates Foundation.

Shigellosis is a heavy burden where clean water and sanitation are scarce. Valneva puts the toll at up to 165 million infections a year, including 62.3 million in children under five, and up to 600,000 deaths annually, making it the second leading cause of fatal diarrhoeal disease worldwide. Antibiotics are losing ground as drug-resistant strains spread, which is why the US Food and Drug Administration granted S4V2 Fast Track designation in 2024.

Valneva is now working through the complete data from both trials to decide how to take the candidate forward, including which dose and schedule to carry into the next stage of testing. Its chief scientific officer, Hanneke Schuitemaker, said the results were encouraging but stressed that further clinical evaluation and optimisation are still needed before the vaccine can move closer to the clinic.