Open AccessRefinement of the CS6-expressing enterotoxigenic Escherichia coli strain B7A human challenge model: A randomized trial
Author(s) -
Kawsar R. Talaat,
Chad K. Porter,
Kayla Jaep,
Christopher Duplessis,
Ramiro L. Gutiérrez,
Milton Maciel,
Brittany M. Adjoodani,
Brittany Feijoo,
Subhra Chakraborty,
Jessica Brubaker,
Stefanie A. Trop,
Mark S. Riddle,
Sabrina S. Joseph,
A. Louis Bourgeois,
Michael G. Prouty
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0239888
Subject(s) - enterotoxigenic escherichia coli , diarrhea , attack rate , medicine , regimen , colony forming unit , immunology , escherichia coli , biology , bacteria , enterotoxin , biochemistry , genetics , epidemiology , gene
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 10 8 or 10 9 colony forming units (cfu) or a 90-minute fast at doses of 10 9 or 10 10 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 10 8 cfu of B7A, overnight fast, or 10 9 cfu, 90-minute fast, 42.9% (3/7) had moderate-severe diarrhea. Higher attack rates (71.4%; 5/7) occurred in subjects receiving 10 9 cfu, overnight fast, or 10 10 cfu, 90-minute fast. Upon rechallenge with 10 9 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.