Valneva SE (Nasdaq: VALN; Euronext Paris: VLA), a specialty vaccine company, announced positive results from two Phase 2 trials of Shigella4V2 (S4V2), the world’s most clinically advanced tetravalent bioconjugate vaccine candidate against shigellosis. Valneva is evaluating the complete dataset of the Phase 2 infant and CHIM trials to determine the most appropriate path forward for the potential first-in-class vaccine candidate.

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 annually are due to Shigella of which 62.3 million occur in children younger than five years¹. Developing an effective vaccine to prevent this deadly disease is a public health imperative for many areas of the world.

The Phase 2 infant trial S4V02 (Identifier: NCT06523231) conducted in Kenya investigated the safety and immunogenicity of two dose levels of S4V2 compared with a control meningococcal vaccine in 110 infants aged nine months. Participants were vaccinated according to a two-dose schedule.

S4V2 showed a favorable safety and tolerability profile across both dose levels evaluated. Most solicited and unsolicited adverse events were mild to moderate in severity and did not differ statistically from the control group. All treatment-related adverse events resolved without complications.

Following the two-dose vaccination schedule, S4V2 induced immune responses with statistically significant increases in anti-LPS IgG antibody levels for all four targeted Shigella serotypes compared with the control group. Geometric Mean antibody Titers peaked after the second dose and remained above baseline levels six months later. Data from this trial provide encouraging evidence of immunogenicity and antibody persistence while highlighting the need for further evaluation of dose selection and vaccination scheduling to optimize the breadth and robustness of the immune response.
The Phase 2 CHIM trial S4V03 (Identifier: NCT06615375), aimed to evaluate the safety, immunogenicity and efficacy of S4V2 in approximately 120 healthy adults aged 18 to 50 years who were seronegative for Shigella at baseline. The trial was conducted across three clinical sites in the United States.

Following confirmation of the selected vaccine dose in Step 1 of the trial, newly enrolled participants received two doses of S4V2 or placebo one month apart. Approximately one month after the second vaccination, participants were challenged with the Shigella sonnei 53G strain to evaluate the vaccine 's ability to confer protection against S. sonnei 53G-associated shigellosis.

The trial met its primary endpoint with a statistically significant reduction in the incidence of shigellosis due to the S. sonnei serotype among participants who received S4V2 compared with those who received placebo. Further analysis of efficacy and immunogenicity are ongoing.

Hanneke Schuitemaker, Ph.D., Chief Scientific Officer of Valneva, commented "These studies provide important clinical data on the safety, immunogenicity and preliminary efficacy of the S4V2 vaccine candidate. The favorable safety profile observed across both studies, together with the immune responses seen in infants and the achievements of the predefined primary endpoint in the CHIM study, represent positive and encouraging results while underscoring the need for further clinical evaluation and optimization. We will complete the assessment of the full datasets to inform the design of the next steps of clinical development for the vaccine candidate."
The U.S. Food and Drug Administration (FDA) granted Fast Track designation to S4V2 in 2024², recognizing its potential to address a serious condition and fill an unmet medical need.

LimmaTech was the sponsor for both trials. Trial S4V02, conducted in infants, was supported by funding from the Gates Foundation.