Every year, diarrhoea kills around 525,000 children under five, mostly in south Asia and sub-Saharan Africa. A synthetic carbohydrate-based vaccine candidate called SF2a-TT15, developed at Institut Pasteur, targets *Shigella flexneri 2a*—one of the most common bacterial causes of this disease. The vaccine was safe and strongly immunogenic in a Phase 1 trial with healthy Israeli adults. This Phase 2a study will test it in the actual target population: first adults, then children aged 2–5 years, and finally infants aged 9 months old. Moving from one age group to the next depends on safety data and independent committee approval. The trial will take place at the Kenya Medical Research Institute in Kericho, with Prof Fredrick Sawe as principal investigator. If successful, this study—combined with an ongoing controlled human infection model—will provide the proof of protection needed for a “GO-NO GO” decision on developing a four-valent *Shigella* vaccine using similar synthetic carbohydrate mimics. A working vaccine would directly reduce childhood deaths and the 7 million Disability-Adjusted Life Years lost to shigellosis each year. It would also strengthen public health infrastructure in the regions that need it most.
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Diarrheal diseases are the second leading cause of death in children under five years old, and are responsible for killing around 525,000 children every year. 80% of the deaths occur in south Asia and sub-Saharan Africa, with a burden cost of more than 7 million Disability-Adjusted Life Years (DAL YS). Over the last 20 years, WHO, UNICEF and more recently the Wei/come trust (WT) and the Bill and Melinda Gates Foundation (BMGF) have supported many possible prevention measures, including vaccination. lnstitut Pasteur has developed a monovalent vaccine candidate against Shigella. flexneri 2a (SF2a), one of the most prevalent S. flexneri serotypes worldwide. The candidate, named SF2a-TT15, is a synthetic carbohydrate-based conjugate vaccine incorporating a functional oligosaccharide (OS) mimic of the 0-antigen (0-Ag), the bacterial outer membrane polysaccharide, coupled to tetanus toxoid (TT). The SF2aTT15 vaccine candidate was shown to be safe and highly immunogenic in a Phase I clinical trial, performed in healthy Israeli adult volunteers (NCT02797236, Cohen eta/. manuscript in preparation). Based on these results, BMGF and WT have decided to support a Phase 2a age descending study (ADS), which aims at making the proof of concept of safety and immunogenicity of SF2a-TT15 in the target population. Basically, parenteral injection of the SF2a-TT15 vaccine candidate will proceed by starting with a first adult cohort, then a 2-5 yr-old children cohort, and eventually a 9mo-o/d infant cohort. Moving from one cohort to the other will be based on safety data and /DMC approval. The doses of the vaccine and the use of alum as an adjuvant will follow the study design of the phase 1 clinical trial, which showed no safety or tolerability issues. lnstitut Pasteur is sponsor for this ADS and the Kenya Medical Research Institute (KEMRI) I Kericho Field Station is the investigator site with Prof Fredrick Sawe being the principal investigator. This clinical study combined to the ongoing controlled human infection model (CHIM) study to provide the proof of concept of protection induced by SF2a-TT15 will give rise to a "GO-NO GO" decision for further development of a 4- va/ent conjugate Shigella vaccine based on the use of synthetic OS mimics.
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