As Shigella outbreaks quietly escalate worldwide, becoming a leading cause of fatal diarrheal illness even in developed nations, a promising vaccine candidate has entered a crucial testing phase.
Shigella is a bacteria that causes shigellosis, an infection characterized by symptoms such as bloody or prolonged diarrhea, abdominal pain, and fever, which can last between five to seven days. In rare instances, shigellosis can lead to more severe complications, including reactive arthritis, bloodstream infections, and seizures.
The disease, which causes an estimated 165 million infections globally, including 62 million cases in children under five, has led to urgent action from vaccine developers.
Recent Centers for Disease Control and Prevention (CDC) data reveals concerning numbers in the United States, with 18,002 cases reported as of the first of November. California leads with 3,864 cases, followed by New York with 2,647 cases. Despite the World Health Organization (WHO) designating shigellosis as a priority concern, the U.S.Food and Drug Administration (FDA) has yet to approve any vaccine against this widespread illness.
However, a significant breakthrough was announced yesterday as Valneva SE and LimmaTech Biologics AG launched their Phase 2b controlled human infection model (CHIM) study for their vaccine candidate, Shigella4V2 (S4V2). This tetravalent bioconjugate vaccine (a vaccine that contains four components), licensed exclusively to Valneva worldwide, represents the most advanced clinical effort to combat shigellosis.
The comprehensive study will involve approximately 120 healthy participants aged 18-50 who have no prior Shigella exposure. Conducted across three U.S. locations, this double-blind, placebo-controlled trial will proceed in two distinct phases. The initial phase will confirm the appropriate vaccine dosage, followed by a challenge phase where participants will be exposed to the Shigella sonnei strain 53G one month after receiving either the vaccine or placebo.
The development effort extends beyond adult trials, with LimmaTech planning to initiate a pediatric study in low and middle-income countries before year-end 2024. Valneva will oversee all subsequent development aspects, including manufacturing and regulatory compliance, as well as global commercialization if approved.
The FDA’s recent Fast Track designation for S4V2 acknowledges the urgent need for effective treatment options against shigellosis. The WHO continues to highlight the endemic nature of the disease in developing countries, with particular concern for Shigella dysenteriae type 1 due to its severe symptoms.
This vaccine development represents a critical step forward in addressing a significant public health challenge that has remained largely under-reported despite its global impact. With the clinical trials now underway, the medical community awaits results that could potentially provide the first approved vaccine against this widespread and dangerous infection.
Commenting on this article, one national Shigella lawyer said, “Because they are not fully potty-trained, shigellosis is very common among toddlers. The result is that family members and friends can also become infected. Positive results from this vaccine trial would be a welcome addition to solving this global health problem.”
