Safety and immunogenicity of ETVAX®, an oral inactivated vaccine against enterotoxigenic Escherichia coli diarrhoea: a double-blinded, randomised, placebo-controlled trial among Finnish travellers to Benin, West-Africa.

BACKGROUND: No licensed human vaccines are available against enterotoxigenic Escherichia coli (ETEC), a major diarrhoeal pathogen affecting children in low and middle-income countries (LMIC) and foreign travellers alike. ETVAX®, a multivalent oral whole-cell vaccine containing four inactivated ETEC strains and the heat-labile enterotoxin B subunit (LTB), has proved promising in Phase 1 and Phase 1/Phase 2 studies.

METHODS: We conducted a Phase 2b double-blinded, randomised, placebo-controlled trial among Finnish travellers to Benin, West-Africa. This report presents study design and safety and immunogenicity data.Volunteers aged 18-65 years were randomised 1:1 to receive ETVAX® or placebo. They visited Benin for 12 days, provided stool and blood samples, and completed adverse event (AE) forms.IgA and IgG antibodies to LTB and O78 lipopolysaccharide (LPS) were measured by electrochemiluminescence.

RESULTS: The AEs did not differ significantly between vaccine (n = 374) and placebo (n = 375) recipients. Of the solicited AEs, loose stools/diarrhoea (26.7%/25.9%) and stomach ache (23.0%/20.0%) were reported most commonly. Of all possibly/probably vaccine-related AEs, the most frequent were gastrointestinal symptoms (54.0%/48.8%) and nervous system disorders (20.3%/25.1%). Serious AEs (SAEs) were recorded for 4.3%/5.6%, all unlikely to be vaccine-related.Among the ETVAX® recipients, LTB-specific IgA antibodies increased 22-fold. For the 370/372 vaccine/placebo recipients, the frequency of ≥2-fold increases against LTB was 81%/2.4%, and against O78 LPS 69%/2.7%. The majority of ETVAX® recipients (93%) responded to either LTB or O78.

CONCLUSIONS: This Phase 2b trial is the largest on ETVAX® undertaken among travellers to date. ETVAX® showed an excellent safety profile and proved strongly immunogenic, which encourages further development of this vaccine.