Shigella4V2 Tetravalent Bioconjugate Vaccine Clinical Trials, Efficacy, Indication, Side Effects
Valneva SE and LimmaTech Biologics AG co-develop Shigella4V2 (S4V2), a second-generation tetravalent bioconjugate vaccine candidate against shigelllosis, a significant public health problem that remains endemic in many developing countries. In 2015, LimmaTech signed a research collaboration agreement with GlaxoSmithKline (GSK) to develop novel, bioconjugate antigen-based vaccines, including a monovalent Shigella vaccine to be developed with the support of the Wellcome Trust. Following positive results from the proof-of-concept clinical trial with the monovalent Shigella vaccine, LimmaTech and GSK initiated the development of a multivalent Shigella vaccine in 2018, funded partly by a Wellcome Trust grant. In July 2023, LimmaTech announced that it had in-licensed the S4V2 Shigella bioconjugate vaccine candidate from GSK to lead the further development of the program. On August 1, 2024, Valneva SE announced that it had entered a strategic partnership and exclusive licensing agreement with LimmaTech to develop, manufacture, and commercialize Shigella4V vaccines.
As of October 16, 2024, the U.S. Food and Drug Administration (FDA) granted Shigella4V Fast Track designation. The anticipated FDA regulatory pathway for S4V2 will leverage a combination of Controlled Human Infection Model studies to support potential initial approval in adults, followed by field efficacy studies to expand the indication to children. On November 13, 2024, Valneva and LimmaTech Biologics announced that the first participant had been vaccinated in a Phase 2b (NCT06615375) controlled human infection model (CHIM) study of Shigella4V2.
In addition to the CHIM study, LimmaTech and Valneva announced on April 9, 2025, that the first participant had been vaccinated in a Phase 2 infant safety and immunogenicity study of Shigella4V2 (S4V2) in Kenya. Sponsored and conducted by LimmaTech, supported by funding from the Gates Foundation, the Phase 2 study S4V02 will test the safety and immunogenicity of S4V2 in nine-month-old infants to identify the best dose to be tested in a Phase 3 trial. This Study's Completion Date is estimated for November 2025.
LimmaTech Bio is an independently owned biotechnology company in Schlieren, Switzerland. In February 2015, GSK acquired it, separating the company from GlycoVaxyn.
Valneva SE is a specialty vaccine company that develops, manufactures, and commercializes prophylactic vaccines for infectious diseases, addressing unmet medical needs. We take a highly specialized and targeted approach, applying our expertise across multiple vaccine modalities. We are focused on providing either first-class, best-in-class, or only-in-class vaccine solutions.
Shigella4V2 Tetravalent Bioconjugate Vaccine Indication
On May 17, 2024, the World Health Organization (WHO) published an updated list of drug-resistant bacteria most threatening to human health to inform the development of new treatments and strategies to prevent and mitigate the spread of antimicrobial resistance. Shigella spp are included in the updated list as high-priority pathogens because of the substantial burden at the community level and increasing levels of resistance. Shigellosis is a global health threat caused by the Gram-negative Shigella spp. bacteria. It is estimated that up to 165 million infections are due to Shigella, of which 62.3 million occur in children younger than five.
Diarrheal infection is one of the significant causes of morbidity and mortality in numerous countries, as well as in travelers and deployed military personnel in endemic regions. The U.S. CDC estimates that about 450,000 Shigella infections occur annually; 242,000 infections are antimicrobial-resistant.
LimmaTech Biologics Multivalent Technology Platform
LimmaTech Biologics developed a proprietary vaccine technology that enables the design of vaccine candidates that contain multiple immunogenic antigens and can be produced in a single and scalable step. A vital aspect of this proprietary technological innovation is engineering an E. coli strain to produce self-adjuvanting vaccine candidates. This technology potentially maximizes a vaccine candidate's potency against the pathogen and provides lasting protection.
LimmaTech Biologics Agreement Valneva SE
Under the agreement with Valneva, LimmaTech will receive an upfront payment of €10 million and be eligible to receive additional regulatory, development, and sales-based milestone payments and low double-digit royalties on sales. LimmaTech will be responsible for conducting a Phase 2 Controlled Human Infection Model and a Phase 2 pediatric study. Both clinical trials are expected to begin in the second half of 2024. Valneva will assume all further development, including chemistry, manufacturing, controls, and regulatory activities, and will be responsible for its commercialization worldwide if the vaccine candidate is approved.
The global market for a vaccine against Shigella is estimated to exceed $500 million annually.
Shigella4V2 Tetravalent Bioconjugate Vaccine News
April 9, 2025 - Dr. Patricia Martin, Chief Operating Officer of LimmaTech, stated in a press release, “We are encouraged by the potential of S4V2 to provide a solution for a serious global health threat and make a profound impact in protecting the health of so many children worldwide.”
February 18, 2025 - Peter Bühler, Valneva’s Chief Financial Officer, commented, “With over €168 million of cash at the end of 2024, we are entering 2025 in a good financial position to support these objectives.”
November 13, 2024—Thomas Lingelbach, CEO of Valneva, commented in a press release, "Human challenge studies are unique in their ability to investigate and understand the onset and development of disease in a safe and highly controlled environment. This CHIM study forms part of our staggered and risk-mitigating development strategy for S4V2, as it should provide the first results on efficacy before potentially advancing to further CHIM and Phase 3 studies."
October 16, 2024: Dr. Franz-Werner Haas, CEO of LimmaTech, released a press release stating, "We are highly encouraged by the FDA's Fast Track designation, which reinforces our efforts and underscores the significant potential of the S4V Shigella vaccine candidate to address a serious global health threat."
August 1, 2024—Thomas Lingelbach, CEO of Valneva, commented in a press release, "We are very pleased to partner with LimmaTech to advance a promising program in an area of high unmet medical need. The Shigella vaccine candidate enables a potential first-in-class vaccine solution for both LMICs and travelers and, as such, represents a potentially highly synergistic product for Valneva. The anticipated development path follows a staggered and risk-mitigated strategy."
February 22, 2024: Patricia Martin, PhD, Chief Operating Officer of LimmaTech, commented: "Shigellosis is a serious disease caused by a pathogen that continuously evolves and becomes increasingly resistant to antibiotics. Our vaccine candidate has the potential to prevent an infection that threatens the lives of many children and protect travelers and military personnel traveling to Shigella-endemic countries. We look forward to continuing its clinical development in a study we plan to initiate in 2024.
July 20, 2023—LimmaTech Biologics AG signed an in-license agreement with GSK, enabling the company to develop and commercialize a quadrivalent bioconjugate vaccine candidate for Shigellosis that GSK added to its infectious disease pipeline when LimmaTech Bio's predecessor company, GlycoVaxyn, was acquired by GSK in 2015.
Shigella4V2 Vaccine Clinical Trial
Following positive Phase 1/2 study results in February 2024, LimmaTech will conduct the Phase 2 study S4V02 (Identifier: NCT06523231), the safety and immunogenicity of the second-generation tetravalent bioconjugate candidate vaccine S4V2 will be tested in approximately 110 nine-month-old infants to identify the best dose to be tested in a Phase 3 trial. Sponsored and conducted by LimmaTech, S4V02 is a randomized, controlled, and blinded study conducted at a single study site in Kenya. Participants will receive a two-dose vaccination with one of two different vaccine dose levels of S4V2 or a control vaccine. Safety will be evaluated throughout the trial for approximately six months following the last vaccination. The study's results, supported by funding from the Gates Foundation, are expected in the second half of 2025.
The Phase I/II clinical study is a randomized, double-blind, dose-finding, and age-descending clinical trial designed to assess the safety and immunogenicity of Shigella4V (S4V). The clinical trial is divided into two parts. The Part 1 age-descending study evaluated the vaccine candidate's safety in adults, children (two to five years), and infants. The Part 2 dose-finding study evaluated S4V's safety and immunogenicity in the nine-month-old target population to identify the preferred vaccine dose. On May 25, 2022, results from the study suggested that the Shigella quadrivalent vaccine offered a promising solution to the morbidity and mortality associated with Shigella infections. Building on previous achievements with conjugate Shigella vaccines, a bioconjugate comprised of Shigella O-antigen coupled to the carrier protein Pseudomonas aeruginosa exoprotein A (EPA) was determined to be a safe, immunogenic, and tolerable vaccine. The study confirmed that transitioning the monovalent S. flexneri 2a vaccine formulation from single valency to multivalency is required to induce immunity against the four major Shigella serotypes.