The Protective Immune Response to Attenuated Enterotoxigenic Escherichia Coli Infection
Condition: Diarrhea
MeSH terms: Infections; Escherichia coli Infections; Diarrhea
Study type: Interventional

Summary: 
      The existing diarrhoeagenic Escherichia coli (E. coli) challenge model is already suitable
      for dietary interventions in its current form, targeted to impact on the immediate clinical
      symptoms upon E. coli infection. In order to make the model also suitable for dietary
      interventions that are aimed at support of the protective response against reinfection, the
      immune response triggered by the primary infection should be suboptimal. The MIRRE pilot
      study is set up to determine how much the primary inoculation dose of diarrheagenic E. coli
      should be lowered in order to result in a reduced protective response upon a secondary
      infection.
    

Detailed description: 
      The MIRRE pilot study is a randomized, double-blind dose-response, parallel 7 weeks human
      infection study. Healthy male subjects, 18-55 years of age who fulfil all of the inclusion
      criteria and none of the exclusion criteria, will be randomly assigned to one of five
      inoculation dosages of a live attenuated diarrheagenic E. coli strain (n=6 per group).
      Subjects will be instructed to maintain their usual pattern of physical activity and their
      habitual food intake, but to reduce and standardize their dietary calcium intake. After a
      standardized evening meal and an overnight fast, subjects will be orally infected on day 14
      and 35 with a live, but attenuated, diarrheagenic E. coli (strain E1392/75-2A; collection
      NIZO food research). Five groups of 6 subjects will be provided one of the following dosages
      at day 14: 1E10 CFU (standard dose); 1E9 CFU; 1E8 CFU; 1E7 CFU or 1E6 CFU of the E.coli
      strain. At study day 35, all subjects will receive a second inoculation of 1E10 CFU of the
      E.coli strain.

      At various time points before and after diarrheagenic E. coli challenges an online diary will
      be kept to record information on stool consistency, frequency and severity of symptoms, and
      blood and stool samples are collected to quantify antibody levels and to quantify fecal
      infection parameters.

      The hypothesis of this pilot study is that the E. coli infection dose at primary inoculation
      determines the outcomes of the protective immune response and the extent of clinical symptoms
      at a secondary inoculation.Therefore the CFA/II-specific IgG antibody response, in relation
      to clinical symptoms, is the main outcome.
    

Intervention name(s): E. coli strain E1392-75-2A dose 1E10 CFU; E. coli strain E1392-75-2A dose 1E9 CFU; E. coli strain E1392-75-2A dose 1E8 CFU; E. coli strain E1392-75-2A dose 1E7 CFU; E. coli strain E1392-75-2A dose 1E6 CFU
Intervention type(s): Biological; Biological; Biological; Biological; Biological
Intervention description(s): Diarrhoeagenic E. coli strain E1392/75-2A serotype O6:H16 belongs to Pathogen class 2 . The strain has a deletion of genes encoding the heat-labile (LT) and heat-stable (ST) toxins and can not produce any toxins. However, it continues to express Colonization Factor Antigen II (CFA/II) and provides 75% protection against challenge with an LT, ST, CFA/II strain; Diarrhoeagenic E. coli strain E1392/75-2A serotype O6:H16 belongs to Pathogen class 2 . The strain has a deletion of genes encoding the heat-labile (LT) and heat-stable (ST) toxins and can not produce any toxins. However, it continues to express Colonization Factor Antigen II (CFA/II) and provides 75% protection against challenge with an LT, ST, CFA/II strain; Diarrhoeagenic E. coli strain E1392/75-2A serotype O6:H16 belongs to Pathogen class 2 . The strain has a deletion of genes encoding the heat-labile (LT) and heat-stable (ST) toxins and can not produce any toxins. However, it continues to express Colonization Factor Antigen II (CFA/II) and provides 75% protection against challenge with an LT, ST, CFA/II strain; Diarrhoeagenic E. coli strain E1392/75-2A serotype O6:H16 belongs to Pathogen class 2 . The strain has a deletion of genes encoding the heat-labile (LT) and heat-stable (ST) toxins and can not produce any toxins. However, it continues to express Colonizat; Diarrhoeagenic E. coli strain E1392/75-2A serotype O6:H16 belongs to Pathogen class 2 . The strain has a deletion of genes encoding the heat-labile (LT) and heat-stable (ST) toxins and can not produce any toxins. However, it continues to express Colonizat
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The MIRRE pilot study is a randomized, double-blind dose-response, parallel human infection study in 30 healthy adults
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Diarrhea; Gastroenteritis; Bacterial Infections; Escherichia Coli Infections; E.coli