New oral vaccine shows strong protection against childhood diarrhoea

Diarrhoeal diseases continue to pose a serious threat to children in low- and middle-income countries. A leading cause of diarrhoea is enterotoxigenic E. coli (ETEC), a gut bacterium that can quickly lead to dehydration and require hospitalisation. Beyond the immediate dehydration risk, repeated bouts of diarrhoea can slow children’s growth, hinder learning, and limit future opportunities. Over time, these early infections can also increase vulnerability to other health problems, shaping a child’s well-being well into adulthood.

The new oral vaccine ETVAX, supported by Global Health EDCTP3’s predecessor programme, EDCTP2, has shown strong protection against these infections. In a large clinical trial in The Gambia, infants who received ETVAX experienced far fewer episodes of moderate-to-severe diarrhoea caused by ETEC. The vaccine works by teaching the immune system to block ETEC bacteria before they can attach to the gut, release toxins, and cause disease. Its design allows it to target more than 90% of ETEC strains circulating in regions with the highest burden of illness.

The Phase IIb trial, funded through the ETEC Vaccine Efficacy project, involved 4,936 children aged 6 to 18 months. In this rigorously controlled study, half the participants received three doses of ETVAX while the other half received placebo doses. All children were then followed for up to two years, with researchers carefully monitoring each diarrhoeal episode and analysing stool samples to determine the cause.

‘For the first time, we have evidence from a large paediatric population that an oral ETEC vaccine can offer real protection in a high‑burden, low‑income setting.’

Prof. Thomas Wierzba, corresponding author of the Lancet study.

Strong protection when it matters most

The trial, coordinated by Scandinavian Biopharma and published in The Lancet Infectious Diseases, showed that children who received the vaccine were about half as likely to develop moderate-to-severe diarrhoea caused by ETEC compared with those who received a placebo.

The protection was even greater among children who did not have certain intestinal parasite infections. In this group, the vaccine prevented 81% of moderate-to-severe ETEC diarrhoea. The study also found that vaccinating children early in life increased its effectiveness. Infants who received their first dose before nine months of age experienced nearly a 68% reduction in ETEC diarrhoea. 

Beyond protecting against ETEC specifically, ETVAX also reduced the overall incidence of moderate-to-severe diarrhoea from all causes by 21% over a two-year period, similar to the protection afforded by rotavirus vaccine against all-cause diarrhoea, which is administered to 40 million children in low- and middle-income countries through UNICEF.

‘We were encouraged to see reductions not only in ETEC‑positive diarrhoea but also in all‑cause moderate‑to‑severe diarrhoea, suggesting broader public‑health benefits.’

Björn Sjöstrand, CEO, Scandinavian Biopharma 

Moving on to Phase III trials

After reviewing the Phase IIb trial results, the European Medicines Agency (EMA) agreed that ETVAX is ready to move forward to a pivotal Phase III clinical trial. These larger studies will confirm whether the vaccine can consistently prevent ETEC diarrhoea across different countries and populations, while also providing additional data on its safety.

If the Phase III trials are successful and the vaccine receives regulatory approval, ETVAX could become an important tool in reducing diarrhoeal disease, particularly among children living in the world’s poorest regions.

‘We are proud to see this project reach such an important milestone. These results provide a critical foundation for advancing into a Phase III study and, if successful, will bring us closer to delivering a much-needed new vaccine to prevent diarrhoeal disease.’

Dr Debora Bade, Project Officer, EDCTP Association

This research was made possible by long-term international support. The ETVAX trial was carried out with funding from the EDCTP2 programme, as well as through contributions from EDCTP Association member countries, such as the UK, through the Medical Research Council.