Stephanie Rossow / CDC
A vaccine that targets a major cause of diarrheal disease in children in low-income countries is safe and induced an immune response in a phase 2 trial, researchers reported this week in The Lancet Infectious Diseases.
The double-blind, placebo-controlled phase 2b trial, conducted in Gambia, was evaluating the safety, immunogenicity, and efficacy of ETVAX, an oral whole-cell vaccine for enterotoxigenic Escherichia coli (ETEC), which causes an estimated 75 diarrhea episodes and up to 42,000 deaths a year in children under five years old in low-income nations. Investigators enrolled children ages six to 18 months to receive ETVAX or placebo at three timepoints (days 1, 15, and 90).
A total of 4,936 children were randomized 1:1 to the ETVAX and placebo arms. The primary end points were serious adverse events and vaccine efficacy against moderate-to-severe ETEC-positive diarrhea (MSD-ETEC), excluding coinfections with other pathogens. The investigators also measured serum antibody response to ETEC colonization factors and heat-labile toxins, which cause severe diarrhea and dehydration.
While several ETEC vaccines are in development, ETVAX, developed by Scandinavian Biopharma, is the most clinically advanced. The study authors said the need for an ETEC vaccine will likely grow, given the predictions of increased ETEC incidence in a warming world.
“An ETEC vaccine could reduce illness and deaths, improve child growth, decrease health-care costs, and curb antimicrobial resistance,” they wrote.
First demonstration of protective efficacy
Serious adverse events occurred in 1.0% of the ETVAX group and 1.3% of the placebo group, with none related to the vaccine. Among the 122 children in whom immunity was assessed, ETVAX increased antibodies to ETEC colonization factors and heat-labile toxins.
Although vaccine efficacy was only 26.6% for the primary end point, it rose to 48.2% against MSD-ETEC regardless of copathogens, and 80.6% when excluding enteroparasitic pathogens. Vaccine efficacy against all MSD-ETEC reached 67.8% when dosing started before age nine months.
“This study provides the first demonstration of induction of protective efficacy by ETVAX in young children who are at risk,” the authors concluded. “These findings support progression to a large, multicountry, phase 3 trial to confirm ETVAX efficacy against ETEC disease in children and to support ETVAX introduction in high-burden settings.”