Enterotoxigenic E. coli vaccine safe, immunogenic in children in early trial

Last Updated: 2019-12-06

By Reuters Staff

NEW YORK (Reuters Health) - An oral, inactivated enterotoxigenic Escherichia coli (ETEC) vaccine (ETVAX) is safe and immunogenic in children, according to a new phase-1/2 trial.

Adding a double-mutant heat-labile enterotoxin (dmLT) as an adjuvant improved immune response, Dr. Ann-Mari Svennerholm of the Gothenburg University Vaccine Research Institute in Sweden and colleagues found.

"The encouraging safety and immunogenicity of ETVAX and benefit of dmLT adjuvant in young children support its further assessment for protective efficacy in children in enterotoxigenic E. coli-endemic areas," they conclude in The Lancet Infectious Diseases.

Diarrhea due to ETEC infection is a major cause of morbidity and mortality in children in low- and middle-income countries, note the authors, who have been investigating ETEC vaccines for more than 20 years.

The ETVAX tested in the current study contains recombinant strains overexpressing the four most common enterotoxigenic colonization factors combined with an LCTBA toxoid, and has been shown to be protective in adults in Sweden and Bangladesh.

The authors tested the vaccine in 430 children, including 130 aged 24 to 59 months, 100 aged 12 to 23 months and 200 aged 6-11 months. Vomiting was the most frequent solicited event, and occurred in 8% of the oldest age group, 13% of the middle group, and 15% of the youngest children.

Most children in the two older age groups showed a mucosal IgA response to the main vaccine antigens. The youngest children had a weaker response to four of the five antigens. The youngest age group had fecal secretory IgA immune responses to all of the vaccine antigens.

Adding dmLT "enhanced the magnitude, breadth, and kinetics . . . of immune responses in infants," Dr. Svennerholm and her team note.

They conclude: "This was a single-centre study in Bangladesh, and we have now initiated a phase 1 study of ETVAX in Zambia that will be followed by a phase 2b study in The Gambia to assess safety, immunogenicity, and protective efficacy of ETVAX in young children in different settings."

The ETVAX avoids toxicity associated with earlier vaccines, and is more immunogenic, Dr. Hyesuk Seo and Dr. Weiping Zhang of the University of Illinois at Urbana-Champaign note in an editorial accompanying the study.

"Encouraging data from this study should move ETVAX forward to efficacy trials. Although the efficacy of ETVAX against ETEC diarrhoea in children in ETEC-endemic regions is yet to be demonstrated, some concerns remain," they write. "ETEC vaccines might not be truly effective if they do not also induce protective immunity against ETEC strains producing heat-stable enterotoxin and broad anti-adhesin immunity against ETEC strains expressing heterogeneous adhesins."

The study had no commercial funding. Dr. Svennerholm is a shareholder of Gotovax, a biotech company that may receive a small royalty on sales of ETVAX if it is commercialized. One of her coauthors is an employee and shareholder of Scandinavian Biopharma Holding, which holds some commercial rights to the vaccine.

Dr. Zhang is developing MecVax, an ETEC multivalent subunit vaccine.

SOURCE: https://bit.ly/2sqsxXn and https://bit.ly/35J5OEd The Lancet Infectious Diseases, online November 19, 2019.