Safety and immunogenicity of a single oral dose of recombinant double mutant heat-labile toxin derived from enterotoxigenic Escherichia coli

Samer S. El-Kamary, Mitchell B. Cohen, Louis Bourgeois, Lillian Van De Verg, Nicole Bauers, Mardi Reymann, Marcela F. Pasetti, Wilbur H. Chen

Research output: Contribution to journalArticle

Abstract

Enterotoxigenic Escherichia coli (ETEC) is a primary cause of traveler's diarrhea for which there is no licensed vaccine. This phase 1 trial determined the safety and immunogenicity of a recombinantly produced double mutant heat-labile enterotoxin (dmLT) of ETEC. It was administered as a single oral dose of dmLT in escalating doses of 5 μg, 25 μg, 50 μg, and 100 μg, followed by a 72-h inpatient observation, outpatient visits at 8, 14, and 28 days, and telephone calls at 2 and 6 months postvaccination. Safety was assessed by frequency of adverse events, and immune responses determined after immunization included dmLT-specific serum IgA and IgG, fecal IgA, antibody-secreting cells (ASC), and antibodies in lymphocyte supernatant (ALS) responses. All doses were well tolerated by the 36 healthy adults enrolled. Immune responses were limited in the 5- and 25-μg dose recipients. The 50-μg dose recipients trended toward stronger responses than the 100-μg dose recipients by serum IgA (67% versus 33%, P = 0.22), serum IgG (58% versus 33%, P = 0.41), and fecal IgA (58% versus 33%, P = 0.41). By day 14 postvaccination, there were significantly more positive responders (≥4-fold increase from baseline) among the 50- versus 100-μg dose recipients for serum IgA (P = 0.036) but not serum IgG (P = 0.21). In conclusion, a single oral dose of dmLT was well tolerated and immunogenic, with immune responses plateauing at the 50-μg dose.

Original languageEnglish (US)
Pages (from-to)1764-1770
Number of pages7
JournalClinical and Vaccine Immunology
Volume20
Issue number11
DOIs
StatePublished - Nov 2013
Externally publishedYes

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Enterotoxigenic Escherichia coli
Immunoglobulin A
Escherichia coli
Hot Temperature
Safety
Serum
Immunoglobulin G
Immunization
Antibody-Producing Cells
Lymphocytes
Antibodies
Enterotoxins
Telephone
Inpatients
Diarrhea
Outpatients
Vaccines
Observation

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Immunology
  • Immunology and Allergy
  • Microbiology (medical)

Cite this

Safety and immunogenicity of a single oral dose of recombinant double mutant heat-labile toxin derived from enterotoxigenic Escherichia coli. / El-Kamary, Samer S.; Cohen, Mitchell B.; Bourgeois, Louis; Van De Verg, Lillian; Bauers, Nicole; Reymann, Mardi; Pasetti, Marcela F.; Chen, Wilbur H.

In: Clinical and Vaccine Immunology, Vol. 20, No. 11, 11.2013, p. 1764-1770.

Research output: Contribution to journalArticle

El-Kamary, Samer S. ; Cohen, Mitchell B. ; Bourgeois, Louis ; Van De Verg, Lillian ; Bauers, Nicole ; Reymann, Mardi ; Pasetti, Marcela F. ; Chen, Wilbur H. / Safety and immunogenicity of a single oral dose of recombinant double mutant heat-labile toxin derived from enterotoxigenic Escherichia coli. In: Clinical and Vaccine Immunology. 2013 ; Vol. 20, No. 11. pp. 1764-1770.
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