Project: Field studies of an oral whole cell ETEC vaccine candidate in African toddlers and children: Assess efficacy, and set parameters for pivotal Phase 3 trials

Acronym	ETEC Vaccine Efficacy (Reference Number: RIA2017S-2024)
Duration	01/01/2019 - 31/12/2022
Project Topic	This project focuses on the clinical evaluation of ETVAX®,a much-needed vaccine against enterotoxigenic Escherichia coli (ETEC) induced diarrhoea. The objectives are to establish the safety and immunogenicity of ETVAX® in infants and young children in Zambia and to explore its protective efficacy in a Phase 2b field trial in The Gambia. ETEC remains a major cause of diarrhoea-associated mortality and morbidity, particularly in Africa. ETEC is also associated with other long-term negative health and economic impacts for children and their families in low-resource areas. Establishing the protective efficacy of promising ETEC vaccine candidates is a high priority for the World Health Organization. Our team of collaborators aims to move ETVAX®, an inactivated whole cell vaccine candidate, into advanced clinical development including field efficacy testing. ETVAX® consists of four E. coli whole cell components, each engineered to over-express key ETEC colonization factors (CFA/I, CS3, CS5, and CS6) and LCTBA, a hybrid protein of the B-subunits of the cholera toxin and ETEC LT toxins. The vaccine will be administered with a mucosal adjuvant, double mutant heat labile toxin (dmLT). Based on studies in Swedish adults, dmLT improved the toxin-neutralizing antibody response as well as antibody and T cell responses to the CS6 component in the vaccine. The selected components in the vaccine are expected to provide 80 to 85 percent coverage of ETEC strains circulating in Africa. The project team will conduct a Phase 1 age descending study in adults, children 10-23 months old and infants 6-9 months to establish the safety and immunogenicity of ETVAX® in Zambia, followed by a Phase 2b protective efficacy study in infants 6 to 18 months of age in The Gambia. The proposed studies address three priority research areas for EDCTP: field testing of vaccines against ETEC; gaining a better understanding of oral vaccine safety, immunogenicity and efficacy in age groups at high risk for ETEC diarrhoea; and developing and testing new approaches and diagnostic tools for more sensitive and rapid detection of ETEC and other enteric pathogens in low-resource settings possibly by using point-of-care nucleic acid testing with remote quality control setup. In addition, the proposed work will strengthen clinical trial and laboratory capabilities in Zambia and The Gambia by providing training in Good Clinical Practices (GCP) and Good Laboratory Practices (GLP), and by introducing relevant microbiology and new immunological technologies needed to support this and future enteric vaccine trials.
Network	EDCTP2
Call	Strategic actions supporting large-scale clinical trials 2017

Project partner

Number	Name	Role	Country
1	Scandinavian Biopharma Holding AB	Coordinator	Sweden
3	Centre for Infectious Disease Research in Zambia Limited	Partner	Zambia
5	London School of Hygiene and Tropical Medicine	Partner	United Kingdom
7	United Medix Laboratories Ltd	Partner	Finland
9	University of Gothenburg	Partner	Sweden