Establishment of a Shigella sonnei human challenge model in Thailand

Abstract

In order to establish a human challenge model of Shigella related disease for vaccine testing, a dose-escalating inpatient trial was performed. Three groups of 12 healthy adult volunteers were orally challenged with 93,440 and 1680 CFU of Shigella sonnei strain 53G. Subjects were admitted to the Vaccine Trial Centre (VTC) at Mahidol University in Bangkok, Thailand. The primary purpose of this study was to identify the dose of S. sonnei 53G required to elicit clinical disease in at least 70% of Thai adult subjects. At the highest dose of 1680 CFU, the attack rate was 75%, while at the two lower doses, the attack rate was approximately 50%. This human challenge model, which is the first of its kind in an endemic region, will provide an opportunity for S. sonnei vaccine evaluation in endemic populations.

Fig. 1

Volunteer screening and enrollment.

Fig. 2

Serum IgA, IgG, and IgM antibody titers (bars represent geometric mean (middle bar) with 95% confidence intervals) against S. sonnei lipopolysaccharide (LPS) of subjects at baseline (closed round symbol), Day 14 (open square symbols) and Day 28 (star symbols) after challenge with S. sonnei 53G at doses of 93, 440 and 1680 colony forming unit (CFU). No significant dose related linear trends were noted.

Fig. 3

IgA, IgG and IgM antibody secreting cells (ASC) counts (bars represent geometric mean (middle bar) with 95% confidence intervals) to S. sonnei lipopolysaccharide (LPS) of subjects at baseline (closed round symbol), Day 7 (open square symbols) and Day 9 (star symbols) after challenge with S. sonnei 53G at doses of 93, 440 and 1680 colony forming unit (CFU). ASCs were determined by ELISPOT. Significant dose related linear trends P values (linear by linear association) are shown.