Valneva: its shigellosis vaccine positive in Phase 2, next steps to be defined

Favorable tolerability in infants, primary endpoint met in adults

Shigellosis is the second leading cause of fatal diarrhea worldwide. According to estimates cited by the company, the Shigella bacterium may cause up to 165 million infections and up to 600,000 deaths per year, amid growing antibiotic resistance.

The first trial, conducted in Kenya among 110 nine-month-old infants, compared two dose levels of S4V2 with a control meningococcal vaccine, using a two-injection schedule. Adverse events, mostly mild to moderate, did not differ statistically from those in the control group, and all treatment-related events resolved without complications.

The vaccine induced a statistically significant increase in anti-LPS IgG antibodies against the four targeted serotypes compared with the control group. Geometric mean titers peaked after the second dose and remained above their initial level six months later.

The second trial, a controlled human infection model (CHIM), involved approximately 120 seronegative adults aged 18 to 50 at three centers in the United States. Exposed to the Shigella sonnei 53G strain about one month after the second injection, vaccinated participants showed a statistically significant reduction in the incidence of shigellosis compared with placebo.

Dose and vaccination schedule still to be assessed before the next steps

This primary endpoint concerns shigellosis linked to the S. sonnei serotype, the only strain used in the challenge trial, whereas S4V2 targets four serotypes. Additional efficacy and immunogenicity analyses are ongoing.

For the pediatric trial, the company stresses the need to further evaluate the choice of dose and the vaccination schedule in order to optimize the magnitude and robustness of the immune response. Its Chief Scientific Officer, Hanneke Schuitemaker, described “positive and encouraging results,” while insisting on “the need for further clinical evaluation and optimization.”

“We will complete the evaluation of all the data in order to guide the design of the next steps of clinical development,” she added. The candidate has held the U.S. FDA’s Fast Track designation since 2024. LimmaTech was the sponsor of both trials, the one conducted in infants having been funded by the Gates Foundation.