In:
PLOS ONE, Public Library of Science (PLoS), Vol. 15, No. 12 ( 2020-12-2), p. e0239888-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0239888
DOI:
10.1371/journal.pone.0239888.g001
DOI:
10.1371/journal.pone.0239888.g002
DOI:
10.1371/journal.pone.0239888.g003
DOI:
10.1371/journal.pone.0239888.g004
DOI:
10.1371/journal.pone.0239888.g005
DOI:
10.1371/journal.pone.0239888.t001
DOI:
10.1371/journal.pone.0239888.t002
DOI:
10.1371/journal.pone.0239888.t003
DOI:
10.1371/journal.pone.0239888.s001
DOI:
10.1371/journal.pone.0239888.s002
DOI:
10.1371/journal.pone.0239888.s003
DOI:
10.1371/journal.pone.0239888.s004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2020
detail.hit.zdb_id:
2267670-3
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