Hyperimmune Bovine Colostral Anti-CS17 Antibodies Protect Against Enterotoxigenic Escherichia coli Diarrhea in a Randomized, Doubled-Blind, Placebo-Controlled Human Infection Model

Stephen J. Savarino, Robin McKenzie, David R. Tribble, Chad K. Porter, Aisling O'Dowd, Stephanie A. Sincock, Steven T. Poole, Barbara Denearing, Colleen M. Woods, Hye Kim, Shannon L. Grahek, Carl Brinkley, Joseph H. Crabb, Louis Bourgeois

Research output: Contribution to journalArticle

Abstract

Enterotoxigenic Escherichia coli (ETEC) commonly cause diarrhea in children living in developing countries and in travelers to those regions. ETEC are characterized by colonization factors (CFs) that mediate intestinal adherence. We assessed if bovine colostral IgG (bIgG) antibodies against a CF, CS17, or antibodies against CsbD, the minor tip subunit of CS17, would protect subjects against diarrhea following challenge with a CS17-expressing ETEC strain. Methods: Adult subjects were randomized (1:1:1) to receive oral bIgG against CS17, CsbD, or placebo. Two days prior to challenge, subjects began dosing 3 times daily with the bIgG products (or placebo). On day 3, subjects ingested 5 × 109 cfu ETEC strain LSN03-016011/A in buffer. Subjects were assessed for diarrhea for 120 hours postchallenge. Results: A total of 36 subjects began oral prophylaxis and 35 were challenged with ETEC. While 50.0% of the placebo recipients had watery diarrhea, none of the subjects receiving anti-CS17 had diarrhea (P =. 01). In contrast, diarrhea rates between placebo and anti-CsbD recipients (41.7%) were comparable (P = 1.0). Conclusions: This is the first study to demonstrate anti-CS17 antibodies provide significant protection against ETEC expressing CS17. More research is needed to better understand why anti-CsbD was not comparably efficacious. Clinical Trials Registration. NCT00524004

Original languageEnglish (US)
Article numberjiz135
Pages (from-to)505-513
Number of pages9
JournalJournal of Infectious Diseases
Volume220
Issue number3
DOIs
StatePublished - Jul 2 2019

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Enterotoxigenic Escherichia coli
Anti-Idiotypic Antibodies
Diarrhea
Placebos
Infection
Immunoglobulin G
Antibodies
Developing Countries
Buffers
Clinical Trials
Research

Keywords

  • antibodies
  • bacterial
  • bacterial vaccines
  • colonization factor antigens
  • controlled human infection model
  • diarrhea
  • Escherichia coli infections
  • fimbriae proteins
  • immunization
  • immunology
  • milk proteins
  • passive
  • prevention and control
  • randomized controlled clinical trial

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Hyperimmune Bovine Colostral Anti-CS17 Antibodies Protect Against Enterotoxigenic Escherichia coli Diarrhea in a Randomized, Doubled-Blind, Placebo-Controlled Human Infection Model. / Savarino, Stephen J.; McKenzie, Robin; Tribble, David R.; Porter, Chad K.; O'Dowd, Aisling; Sincock, Stephanie A.; Poole, Steven T.; Denearing, Barbara; Woods, Colleen M.; Kim, Hye; Grahek, Shannon L.; Brinkley, Carl; Crabb, Joseph H.; Bourgeois, Louis.

In: Journal of Infectious Diseases, Vol. 220, No. 3, jiz135, 02.07.2019, p. 505-513.

Research output: Contribution to journalArticle

Savarino, SJ, McKenzie, R, Tribble, DR, Porter, CK, O'Dowd, A, Sincock, SA, Poole, ST, Denearing, B, Woods, CM, Kim, H, Grahek, SL, Brinkley, C, Crabb, JH & Bourgeois, L 2019, 'Hyperimmune Bovine Colostral Anti-CS17 Antibodies Protect Against Enterotoxigenic Escherichia coli Diarrhea in a Randomized, Doubled-Blind, Placebo-Controlled Human Infection Model', Journal of Infectious Diseases, vol. 220, no. 3, jiz135, pp. 505-513. https://doi.org/10.1093/infdis/jiz135
Savarino, Stephen J. ; McKenzie, Robin ; Tribble, David R. ; Porter, Chad K. ; O'Dowd, Aisling ; Sincock, Stephanie A. ; Poole, Steven T. ; Denearing, Barbara ; Woods, Colleen M. ; Kim, Hye ; Grahek, Shannon L. ; Brinkley, Carl ; Crabb, Joseph H. ; Bourgeois, Louis. / Hyperimmune Bovine Colostral Anti-CS17 Antibodies Protect Against Enterotoxigenic Escherichia coli Diarrhea in a Randomized, Doubled-Blind, Placebo-Controlled Human Infection Model. In: Journal of Infectious Diseases. 2019 ; Vol. 220, No. 3. pp. 505-513.
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abstract = "Enterotoxigenic Escherichia coli (ETEC) commonly cause diarrhea in children living in developing countries and in travelers to those regions. ETEC are characterized by colonization factors (CFs) that mediate intestinal adherence. We assessed if bovine colostral IgG (bIgG) antibodies against a CF, CS17, or antibodies against CsbD, the minor tip subunit of CS17, would protect subjects against diarrhea following challenge with a CS17-expressing ETEC strain. Methods: Adult subjects were randomized (1:1:1) to receive oral bIgG against CS17, CsbD, or placebo. Two days prior to challenge, subjects began dosing 3 times daily with the bIgG products (or placebo). On day 3, subjects ingested 5 × 109 cfu ETEC strain LSN03-016011/A in buffer. Subjects were assessed for diarrhea for 120 hours postchallenge. Results: A total of 36 subjects began oral prophylaxis and 35 were challenged with ETEC. While 50.0{\%} of the placebo recipients had watery diarrhea, none of the subjects receiving anti-CS17 had diarrhea (P =. 01). In contrast, diarrhea rates between placebo and anti-CsbD recipients (41.7{\%}) were comparable (P = 1.0). Conclusions: This is the first study to demonstrate anti-CS17 antibodies provide significant protection against ETEC expressing CS17. More research is needed to better understand why anti-CsbD was not comparably efficacious. Clinical Trials Registration. NCT00524004",
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AU - Savarino, Stephen J.

AU - McKenzie, Robin

AU - Tribble, David R.

AU - Porter, Chad K.

AU - O'Dowd, Aisling

AU - Sincock, Stephanie A.

AU - Poole, Steven T.

AU - Denearing, Barbara

AU - Woods, Colleen M.

AU - Kim, Hye

AU - Grahek, Shannon L.

AU - Brinkley, Carl

AU - Crabb, Joseph H.

AU - Bourgeois, Louis

PY - 2019/7/2

Y1 - 2019/7/2

N2 - Enterotoxigenic Escherichia coli (ETEC) commonly cause diarrhea in children living in developing countries and in travelers to those regions. ETEC are characterized by colonization factors (CFs) that mediate intestinal adherence. We assessed if bovine colostral IgG (bIgG) antibodies against a CF, CS17, or antibodies against CsbD, the minor tip subunit of CS17, would protect subjects against diarrhea following challenge with a CS17-expressing ETEC strain. Methods: Adult subjects were randomized (1:1:1) to receive oral bIgG against CS17, CsbD, or placebo. Two days prior to challenge, subjects began dosing 3 times daily with the bIgG products (or placebo). On day 3, subjects ingested 5 × 109 cfu ETEC strain LSN03-016011/A in buffer. Subjects were assessed for diarrhea for 120 hours postchallenge. Results: A total of 36 subjects began oral prophylaxis and 35 were challenged with ETEC. While 50.0% of the placebo recipients had watery diarrhea, none of the subjects receiving anti-CS17 had diarrhea (P =. 01). In contrast, diarrhea rates between placebo and anti-CsbD recipients (41.7%) were comparable (P = 1.0). Conclusions: This is the first study to demonstrate anti-CS17 antibodies provide significant protection against ETEC expressing CS17. More research is needed to better understand why anti-CsbD was not comparably efficacious. Clinical Trials Registration. NCT00524004

AB - Enterotoxigenic Escherichia coli (ETEC) commonly cause diarrhea in children living in developing countries and in travelers to those regions. ETEC are characterized by colonization factors (CFs) that mediate intestinal adherence. We assessed if bovine colostral IgG (bIgG) antibodies against a CF, CS17, or antibodies against CsbD, the minor tip subunit of CS17, would protect subjects against diarrhea following challenge with a CS17-expressing ETEC strain. Methods: Adult subjects were randomized (1:1:1) to receive oral bIgG against CS17, CsbD, or placebo. Two days prior to challenge, subjects began dosing 3 times daily with the bIgG products (or placebo). On day 3, subjects ingested 5 × 109 cfu ETEC strain LSN03-016011/A in buffer. Subjects were assessed for diarrhea for 120 hours postchallenge. Results: A total of 36 subjects began oral prophylaxis and 35 were challenged with ETEC. While 50.0% of the placebo recipients had watery diarrhea, none of the subjects receiving anti-CS17 had diarrhea (P =. 01). In contrast, diarrhea rates between placebo and anti-CsbD recipients (41.7%) were comparable (P = 1.0). Conclusions: This is the first study to demonstrate anti-CS17 antibodies provide significant protection against ETEC expressing CS17. More research is needed to better understand why anti-CsbD was not comparably efficacious. Clinical Trials Registration. NCT00524004

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KW - Escherichia coli infections

KW - fimbriae proteins

KW - immunization

KW - immunology

KW - milk proteins

KW - passive

KW - prevention and control

KW - randomized controlled clinical trial

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