Refinement of the CS6-expressing enterotoxigenic Escherichia coli strain B7A human challenge model: A randomized trial

Kawsar R. Talaat*, Chad K. Porter, Kayla M. Jaep, Christopher A. Duplessis, Ramiro L. Gutierrez, Milton Maciel, Brittany Adjoodani, Brittany Feijoo, Subhra Chakraborty, Jessica Brubaker, Stefanie A. Trop, Mark S. Riddle, Sabrina S. Joseph, A. Louis Bourgeois, Michael G. Prouty

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Background Human challenge models for enterotoxigenic Escherichia coli (ETEC) facilitate vaccine down-selection. The B7A (O148:H28 CS6+LT+ST+) strain is important for vaccine development. We sought to refine the B7A model by identifying a dose and fasting regimen consistently inducing moderate-severe diarrhea. Methods An initial cohort of 28 subjects was randomized (1:1:1:1) to receive B7A following an overnight fast at doses of 108 or 109 colony forming units (cfu) or a 90-minute fast at doses of 109 or 1010 cfu. A second cohort included naïve and rechallenged subjects who had moderate-severe diarrhea and were given the target regimen. Immune responses to important ETEC antigens were assessed. Results Among subjects receiving 108 cfu of B7A, overnight fast, or 109 cfu, 90-minute fast, 42.9% (3/7) had moderate-severe diarrhea. Higher attack rates (71.4%; 5/7) occurred in subjects receiving 109 cfu, overnight fast, or 1010 cfu, 90-minute fast. Upon rechallenge with 109 cfu of B7A, overnight fast, 5/11 (45.5%) had moderate-severe diarrhea; the attack rate among concurrently challenge naïve subjects was 57.9% (11/19). Anti-CS6, O148 LPS and LT responses were modest across all groups. Conclusions An overnight fast enabled a reduction in the B7A inoculum dose; however, the attack rate was inconsistent and protection upon rechallenge was minimal.

Original languageEnglish
Article numbere0239888
JournalPLoS ONE
Issue number12 December
StatePublished - Dec 2020
Externally publishedYes


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