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Refinement of the CS6-expressing enterotoxigenic Escherichia coli strain B7A human challenge model: A randomized trial.
Talaat, Kawsar R; Porter, Chad K; Jaep, Kayla M; Duplessis, Christopher A; Gutierrez, Ramiro L; Maciel, Milton; Adjoodani, Brittany; Feijoo, Brittany; Chakraborty, Subhra; Brubaker, Jessica; Trop, Stefanie A; Riddle, Mark S; Joseph, Sabrina S; Bourgeois, A Louis; Prouty, Michael G.
Afiliación
  • Talaat KR; Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United States of America.
  • Porter CK; Naval Medical Research Center, Silver Spring, MD, United States of America.
  • Jaep KM; Henry M. Jackson Foundation, Bethesda, MD, United States of America.
  • Duplessis CA; Naval Medical Research Center, Silver Spring, MD, United States of America.
  • Gutierrez RL; Naval Medical Research Center, Silver Spring, MD, United States of America.
  • Maciel M; Henry M. Jackson Foundation, Bethesda, MD, United States of America.
  • Adjoodani B; Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United States of America.
  • Feijoo B; Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United States of America.
  • Chakraborty S; Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United States of America.
  • Brubaker J; Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United States of America.
  • Trop SA; Henry M. Jackson Foundation, Bethesda, MD, United States of America.
  • Riddle MS; Naval Medical Research Center, Silver Spring, MD, United States of America.
  • Joseph SS; Uniformed Services University of the Health Sciences, Bethesda, MD, United States of America.
  • Bourgeois AL; Henry M. Jackson Foundation, Bethesda, MD, United States of America.
  • Prouty MG; Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United States of America.
PLoS One ; 15(12): e0239888, 2020.
Article en En | MEDLINE | ID: mdl-33264302
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vacunas contra Escherichia coli / Proteínas de Escherichia coli / Diarrea / Infecciones por Escherichia coli / Escherichia coli Enterotoxigénica / Antígenos Bacterianos Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Adolescent / Adult / Female / Humans / Male / Middle aged Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vacunas contra Escherichia coli / Proteínas de Escherichia coli / Diarrea / Infecciones por Escherichia coli / Escherichia coli Enterotoxigénica / Antígenos Bacterianos Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Adolescent / Adult / Female / Humans / Male / Middle aged Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos