Shigella4V Tetravalent Bioconjugate Vaccine Clinical Trials, Efficacy, Indication, Side Effects
Valneva SE and LimmaTech Biologics AG are co-developing Shigella4V (S4V), a tetravalent bioconjugate vaccine candidate against Shigellosis. 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 S4V Shigella bioconjugate vaccine candidate from GSK to lead the further development of the program. On August 1, 2024, Valneva SE announced that it 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 S4V 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, the world’s most clinically advanced tetravalent bioconjugate shigellosis vaccine candidate. In addition to the CHIM study, LimmaTech will conduct a Phase 2 pediatric study in Low- and Middle-Income Countries, which is expected to begin before the end of 2024. Valneva will assume all further development, including CMC (chemistry, manufacturing, and controls) and regulatory activities, and be responsible for its commercialization worldwide if approved.
LimmaTech Bio is an independently owned biotechnology company in Schlieren, Switzerland, that spun out from GlycoVaxyn after its acquisition by GSK in February 2015.
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 deep expertise across multiple vaccine modalities, and are focused on providing either first-, best-, or only-in-class vaccine solutions.
Shigella4V 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. 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 be responsible for its commercialization worldwide if the vaccine candidate is approved.
Shigella4V Tetravalent Bioconjugate Vaccine News
November 13, 2024 - Thomas Lingelbach, Chief Executive Officer 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, stated in a press release, "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, Chief Executive Officer 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 continuously evolving and becoming 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.
Shigella4V (S4V) Vaccine Clinical Trial
Following positive Phase 1/2 study results in February 2024, LimmaTech will conduct a Phase 2 Controlled Human Infection Model study (CHIM) in the U.S. and a Phase 2 pediatric study. Valneva will assume responsibility for all further development, including chemistry, manufacturing, controls, and regulatory activities, and will be responsible for its commercialization worldwide.
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.
