A new human challenge model for testing heat-stable toxin-based vaccine candidates for enterotoxigenic Escherichia coli diarrhea dose optimization, clinical outcomes, and CD4+ T cell responses

摘要

Enterotoxigenic Escherichia coli (ETEC) is a common cause of diarrheal illness in young children living in low- and middle-income countries and in travelers to these countries. Several ETEC vaccine candidates are currently being developed, but so far, no broadly protective vaccines have been licensed. Since most moderate and severe ETEC diarrheal episodes are caused by strains that express the heat-stable enterotoxin (ST), ST represents a promising vaccine target. Here we present a human challenge model that can be used to estimate the protective efficacy of ST-based vaccine candidates in clinical vaccine trials. The model is based on the epidemiologically relevant ST-only ETEC strain TW10722, which we show is safe to ingest by volunteers and readily induce diarrhea.