First vaccine against childhood E. coli diarrhea advances toward global use

Overview

Updated May 30

Enterotoxigenic Escherichia coli, or ETEC, causes roughly 220 million episodes of diarrhea annually and kills tens of thousands of children under five—mostly in low-income countries where clean water remains scarce. No vaccine against it has ever been licensed.

On February 16, 2026, The Lancet Infectious Diseases published results from a trial of an oral vaccine called ETVAX. The vaccine cut moderate-to-severe ETEC diarrhea by 48 percent in nearly 5,000 Gambian children, and by 68 percent in infants vaccinated before nine months of age.

The trial, the largest ever conducted for an ETEC vaccine in children, clears the path for a phase 3 study that the European Medicines Agency has already approved. If that succeeds, ETVAX would become the first licensed vaccine against one of the deadliest gut infections in the developing world. Researchers at the University of Gothenburg in Sweden have spent more than a decade trying to close this gap.

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Key Indicators

48%

Reduction in moderate-to-severe ETEC diarrhea

Efficacy across all children when co-infections with common gut pathogens were included

68%

Efficacy in infants under 9 months

Protection was strongest in the youngest age group, which bears the highest disease burden

4,936

Children enrolled in trial

The largest-ever efficacy trial of an ETEC vaccine in a pediatric population

75M

Annual ETEC cases in children under 5

ETEC is among the top five pathogens causing diarrheal death in young children globally

5,800

Infants planned for phase 3 trial

A pivotal phase 3 study in low- and middle-income countries has been approved by the European Medicines Agency

Voices

Curated perspectives — historical figures and your fellow readers.

Ever wondered what historical figures would say about today's headlines?

People Involved

Ann-Mari Svennerholm

Immunologist, University of Gothenburg

Lead developer of ETVAX; overseeing phase 3 preparation

Jahangir Hossain

Lead Author, Phase 2b Trial

Principal investigator at MRC Gambia

Firdausi Qadri

Director, Centre for Vaccine Sciences, icddr,b

Led earlier ETVAX trials in Bangladesh

Organizations Involved

Scandinavian Biopharma

Pharmaceutical Company

Preparing pivotal phase 3 trial

A Stockholm-based pharmaceutical company that develops and manufactures ETVAX in partnership with the University of Gothenburg.

University of Gothenburg

Research University

Originator of ETVAX vaccine technology

The Swedish university where ETVAX was invented, building on a decades-long tradition of oral vaccine research that also produced the world's first licensed oral cholera vaccine.

MRC Unit The Gambia at LSHTM

Research Institute

Conducted the phase 2b field trial

A Medical Research Council unit in Banjul, The Gambia, affiliated with the London School of Hygiene and Tropical Medicine, that served as the implementing organization for the landmark phase 2b trial.

Timeline

January 1991 February 2026

11 events Latest: February 20th, 2026 · 7 months ago Showing 8 of 11

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February 2026
Scandinavian Biopharma confirms phase 3 readiness
Latest Announcement

Following the Lancet publication, Scandinavian Biopharma announces it is prepared to launch a pivotal phase 3 trial enrolling approximately 5,800 infants aged six to nine months across multiple low- and middle-income countries.
February 20th, 2026
Phase 2b results published in The Lancet Infectious Diseases
Publication

The landmark trial shows ETVAX reduced moderate-to-severe ETEC diarrhea by 48 percent across all children and by 68 percent in infants under nine months. The results support advancement to a phase 3 trial enrolling 5,800 infants.
February 16th, 2026
January 2025
European Medicines Agency approves advancement to phase 3
Regulatory

Following formal scientific advice review, the European Medicines Agency concludes that accumulated safety, immunogenicity, and efficacy data support a pivotal phase 3 program.
January 1st, 2025
January 2023
Safety trial completed in Finnish travelers to West Africa
Clinical Trial

A separate placebo-controlled trial tests ETVAX in Finnish adults traveling to Benin, expanding the vaccine's safety and immunogenicity data to a traveler population.
January 1st, 2023
June 2022
Gambia trial completes enrollment of 4,936 children
Clinical Trial

Enrollment closes after nearly 5,000 children are randomized to receive either three doses of ETVAX or placebo, followed by a two-year surveillance period for diarrheal episodes.
June 24th, 2022
February 2021
Landmark phase 2b trial begins enrolling children in The Gambia
Clinical Trial

The MRC Unit The Gambia begins screening and enrolling children aged six to 18 months across four sites in rural Gambia for the largest-ever ETEC vaccine efficacy trial in a pediatric population.
February 22nd, 2021
September 2020
U.S. Army signs development agreement for traveler's diarrhea use
Partnership

Scandinavian Biopharma enters into an agreement with the United States Army Medical Research Acquisition Activity to support ETVAX production, reflecting military interest in preventing diarrhea among deployed soldiers.
September 1st, 2020
November 2019
Phase 1/2 trial demonstrates safety in Bangladeshi children and infants
Clinical Trial

Firdausi Qadri's team at icddr,b tests ETVAX in 495 Bangladeshi participants including young children, marking the vaccine's first pediatric trial. Results are published in The Lancet Infectious Diseases.
November 1st, 2019
January 2018
Phase 1 trial in Bangladeshi adults confirms safety in endemic setting
Clinical Trial

The first test of ETVAX in a country where ETEC is common shows the vaccine is well tolerated and immunogenic in Bangladeshi adults, with or without an immune-boosting adjuvant.
January 1st, 2018
January 2014
ETVAX passes first safety trial in Swedish adults
Clinical Trial

A phase 1 study in 95 healthy Swedish volunteers confirms the vaccine is safe and generates immune responses against ETEC antigens.
January 1st, 2014
January 1991
Gothenburg team's oral cholera vaccine Dukoral licensed
Foundation

Jan Holmgren's group at the University of Gothenburg achieves the first internationally licensed oral cholera vaccine, establishing the scientific foundation for oral enteric vaccines including ETVAX.
January 1st, 1991

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Scenarios

Phase 3 succeeds, ETVAX becomes first licensed ETEC vaccine

Possible

Discussed by: The Lancet Infectious Diseases editorial board, Scandinavian Biopharma, and the European Medicines Agency (which has already provided scientific advice supporting phase 3 advancement)

The pivotal phase 3 trial in 5,800 infants confirms the efficacy signal seen in infants under nine months, meeting its primary endpoint. ETVAX receives regulatory approval and enters routine immunization programs in high-burden countries, potentially preventing millions of diarrheal episodes annually. This is the scenario the developers are actively preparing for, with EDCTP funding secured and EMA alignment in place.

Phase 3 shows modest efficacy, narrower approval follows

Possible

Discussed by: Vaccine researchers who note the phase 2b primary endpoint was not met and that efficacy varied significantly by age group and co-infection status

The phase 3 trial replicates the pattern seen in The Gambia: strong protection in the youngest infants but weaker overall efficacy when older children and those with parasitic co-infections are included. Regulators approve ETVAX for a narrower age window of six to nine months, limiting but not eliminating its public health impact. This mirrors the experience of rotavirus vaccines, which showed lower but still meaningful efficacy in low-income settings.

Phase 3 fails to meet primary endpoint, ETVAX development stalls

Unlikely

Discussed by: Skeptics in the vaccine research community who note that the phase 2b trial did not meet its own primary endpoint and that environmental enteropathy and parasite co-infections may fundamentally limit oral vaccine performance in the populations that need it most

The phase 3 trial, conducted in a broader set of low- and middle-income countries with varying pathogen exposures, fails to demonstrate statistically significant protection. ETVAX joins a long list of promising enteric vaccine candidates that could not clear the final efficacy hurdle in the field. Development continues with reformulated versions or alternative delivery strategies, but licensure is delayed by years.

Competing ETEC vaccine candidates advance, reshaping the field

Possible

Discussed by: Researchers tracking ACE527 (a live attenuated ETEC vaccine) and newer subunit approaches targeting ETEC adhesins and enterotoxins

Regardless of ETVAX's phase 3 outcome, other ETEC vaccine candidates advance into late-stage trials. ACE527, a live attenuated vaccine mixture, or newer subunit approaches could offer higher efficacy or simpler dosing. The field matures from a single frontrunner into a competitive landscape, similar to how multiple rotavirus vaccines eventually reached the market.

Historical Context

3 moments from history that rhyme with this story — and how they unfolded.

1991

Dukoral oral cholera vaccine (1991)

Jan Holmgren at the University of Gothenburg developed Dukoral, the first internationally licensed oral cholera vaccine. The vaccine used inactivated cholera bacteria combined with a cholera toxin B subunit and showed 85 to 90 percent efficacy in the first six months after vaccination in trials across Bangladesh, Peru, and Mozambique.

Then

Dukoral was licensed first in Scandinavia, then internationally, providing three years of immune protection against cholera.

Now

Through technology transfer, Dukoral's approach spawned lower-cost oral cholera vaccines like Shanchol, which became the backbone of the World Health Organization's global cholera vaccine stockpile. The same Gothenburg mucosal immunology group that created Dukoral went on to develop ETVAX.

Why this matters now

ETVAX is a direct scientific descendant of Dukoral, built on the same University of Gothenburg platform for oral mucosal vaccination. Its development demonstrates how foundational research in one enteric disease can enable vaccines for related pathogens decades later.

2006-present

Rotavirus vaccine introduction (2006-present)

In 2006, two rotavirus vaccines were licensed after decades of development. Rotavirus caused roughly 500,000 child deaths annually before vaccination. Nicaragua became the first low-income country to introduce the vaccine the same year as the United States.

Then

Countries that adopted the vaccine saw rotavirus hospitalizations drop by a median of 59 percent within years of introduction.

Now

By 2019, rotavirus vaccines had saved an estimated 140,000 children's lives. More than 120 countries now include them in routine immunization programs, though efficacy is lower in low-income settings where the disease burden is highest.

Why this matters now

ETVAX faces the same challenge rotavirus vaccines encountered: demonstrating sufficient efficacy in the low-income, high-burden populations where the vaccine is most needed, where gut infections and malnutrition can blunt immune responses to oral vaccines.

1960s-present

Oral polio vaccine global rollout (1960s-2020s)

Albert Sabin's oral polio vaccine, licensed in the early 1960s, became the primary tool for global polio eradication. Its oral delivery made mass vaccination campaigns feasible in low-resource settings where injectable vaccines were logistically impractical.

Then

Wild polio cases dropped from an estimated 350,000 annually in 1988 to fewer than 100 per year by the 2020s.

Now

The oral polio vaccine demonstrated that oral immunization could achieve population-level disease control in the developing world, though lower efficacy in tropical settings required more doses and supplementary campaigns.

Why this matters now

ETVAX's oral delivery strategy reflects lessons learned from oral polio vaccination: oral vaccines are far easier to deploy in low-resource settings, but their performance in tropical, high-pathogen environments is consistently lower than in temperate climates, a challenge ETVAX must also overcome.