Abstract
Vaccine studies for Shigella flexneri and enterotoxigenic Escherichia coli have been impaired by the lack of optimal animal models. We used two murine models to show that a S. flexneri 2a bivalent vaccine (CVD 1208S-122) expressing enterotoxigenic Escherichia coli colonization factor antigen-I (CFA/I) and the binding subunits A2 and B of heat labile-enterotoxin (LTb) is immunogenic and protects against weight loss and diarrhea. These findings document the immunogenicity and pre-clinical efficacy effects of CVD 1208S-122 vaccine and suggest that further work can help elucidate relevant immune responses and ultimately its clinical efficacy in humans.
Highlights
Shigella flexneri and enterotoxigenic Escherichia coli (ETEC) are two major bacterial pathogens responsible for substantial burdens of diarrhea in children from developing countries[1,2]
In order to provide stronger evidence of its pre-clinical effects, we evaluated whether CVD 1208S-122 could induce antibody responses and confer protection against diarrhea and weight loss using two murine models of orally administered S. flexneri and ETEC infections in C57BL/6 mice[9,10]
We first tested whether vaccination would be tolerated and prevent disease outcomes—weight loss and diarrhea—after infections with either S. flexneri 2457T or ETEC H10407 in mice fed a normal diet
Summary
Shigella flexneri and enterotoxigenic Escherichia coli (ETEC) are two major bacterial pathogens responsible for substantial burdens of diarrhea in children from developing countries[1,2]. In order to provide stronger evidence of its pre-clinical effects, we evaluated whether CVD 1208S-122 could induce antibody responses and confer protection against diarrhea and weight loss using two murine models of orally administered S. flexneri and ETEC infections in C57BL/6 mice[9,10]. Following antibiotic treatment, these models enable the study of clinical outcomes that mimic human disease in children induced by oral infection and enable the testing of interventions. We used antibiotic pre-treated nourished mice as they closely mimic the disease most often seen in humans with optimal, self-limited diarrhea and weight decrements as reported[6,7]
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