Currently no vaccines to prevent infections from Shigella and ETEC are available. These two pathogens are the leading causes of bacterial diarrhoeal diseases worldwide, affecting up to half of travellers to developing countries. In low- and middle-income countries, Shigella and ETEC have been estimated to cause 200 million diarrhoea cases in children under five years of age, and repeated infections with these pathogens can also have long-term consequences on children growth and development.
The published manuscript describes the evaluation of ShigETEC, a live, attenuated vaccine candidate given orally (drinkable), in a two-staged, randomized, double-blind and placebo-controlled Phase I clinical trial. ShigETEC is based on an engineered Shigella vaccine strain that lacks invasiveness into gut epithelial cells, a hallmark of shigellosis, and also lacks sugar antigens on the bacterial surface that drive narrow-spectrum immune responses. In addition, the vaccine strain carries ETEC antigens expected to induce protective antibodies that inactivate powerful diarrheagenic toxins. The maximum tolerated dose was determined with single doses of increasing amounts of vaccine, while multiple immunizations (two, three and four) with a fixed dose were administered with 3-day interval determined based on the duration of the shedding of the vaccine. The data demonstrate that oral immunization with ShigETEC was well tolerated and safe across the different dose groups tested. ShigETEC induced robust systemic immune responses (serum antibodies) against the Shigella vaccine strain as well as mucosal immunity. Anti-ETEC toxin antibodies were detected primarily in the 4-times immunized cohort and correlated with toxin neutralizing capacity.