Campylobacter Jejuni Challenge Model Development: Assessment of Homologous Protection
Campylobacter Jejuni Challenge Model Development: Assessment of Homologous Protection
The goal of this research is to continue to develop a model of infection with Campylobacter
 jejuni, a bacterium that causes food and water-borne disease (mainly diarrhea). The
 objectives are to 1) determine if healthy subjects develop short-term (<6 month) protection
 to reinfection with C. jejuni; and 2) characterize the immune responses to C. jejuni
 infection. Information obtained will be used in development of a vaccine against
 Campylobacter infections.

 Volunteers will be screened for eligibility within 60 days prior to enrollment. Screening
 will include obtaining informed consent prior to any study procedure. This will be followed
 by medical history, physical examination, review of current medications, blood samples for
 safety labs (WBC, Hct, Hgb, platelet count; chemistry panel; screening for HIV, HLA-B27, HBV,
 and HCV); urine pregnancy testing for females. Stool will be tested for infection.

 Eligible volunteers will be enrolled in the study and admitted to the GCRC on Day -1. They
 will drink a measured dose of C. jejuni on Day 0, and followed for approximately 9 inpatient
 days, during which time the investigators expect at least 75% to develop a diarrheal illness,
 which will be promptly treated with replacement fluids (oral or IV, as indicated) and
 antibiotics. During the inpatient period, subjects will be assessed for any adverse events,
 and blood and stool specimens will be analyzed for markers of infection and markers of immune
 response. Subjects must have resolved or resolving symptoms and two negative stool cultures
 ≥12 hours apart to be eligible for discharge, and will be seen in outpatient follow-up at 21,
 28, 35, 60, and 90 days for additional AE assessments and blood and stool analysis.

 Eight subjects will return for redosing approximately 98 days after the initial dose, with
 the same inpatient and outpatient follow-up as above. Few or none should develop a diarrheal
 illness. Four naïve (previously unexposed) subjects will also receive the dose on Day 98 to
 confirm a 75% illness rate with this dose. They will be followed as the initial group was.
 All participants will be assessed by phone 6 months after the final dose they received.
Inclusion Criteria:

 -  Male or female between 18 and 50 years of age, inclusive.

 -  General good health, without significant medical illness, abnormal physical
 examination findings or clinical laboratory abnormalities as determined by principal
 investigator or principal investigator in consultation with the medical monitor and
 sponsor.

 -  Demonstrate comprehension of the protocol procedures and knowledge of Campylobacter
 illness by passing a written examination (pass grade ≥ 70%)

 -  Willing to participate after informed consent obtained.

 -  Available for all planned follow-up visits, and remain available for medical
 interview/physical exam and monitoring for 90 days post-challenge (last challenge
 received), and a final telephone interview 180 days post-challenge.

 -  Negative urine pregnancy test at screening and a negative urine pregnancy test on the
 day of admittance to the inpatient phase for all female subjects. In addition, female
 subjects will be advised of the need for an effective means of birth control during
 the entire study period.

 Exclusion Criteria:

 -  Presence of a significant medical condition (e.g., psychiatric conditions;
 gastrointestinal disease, such as peptic ulcer, symptoms or evidence of active
 gastritis, inflammatory bowel disease, irritable bowel syndrome; alcohol or illicit
 drug abuse/dependency), or other laboratory abnormalities which in the opinion of the
 investigator precludes participation in the study.

 -  Immunosuppressive illness, IgA deficiency (below the normal limits), or H2
 antihistamine use within 48 h of admission or during inpatient period.

 -  Positive serology results for HIV, HBsAg, or HCV antibodies.

 -  Significant abnormalities in screening lab hematology, serum chemistry, as determined
 by PI or PI in consultation with the medical monitor and sponsor.

 -  Use of any medication known to affect the immune function (e.g., corticosteroids and
 others) within 30 days preceding receipt of the challenge inoculum or planned use
 during the active study period.

 -  Nursing mother on the day of admittance to the inpatient phase for all female
 subjects.

 -  Are not capable of fully informed consent (e.g., cannot read or write English)

 -  Personal or documented family history of an inflammatory arthritis such as reactive
 arthritis, Reiter's syndrome, ankylosing spondylitis, rheumatoid arthritis, or
 Guillain-Barré syndrome (would not include osteoarthritis or vague history of
 arthritis in a relative late in adulthood).

 -  Evidence of neurologic abnormalities (specifically extremity weakness, abnormal deep
 tendon reflexes, symmetric sensory abnormalities - vibratory, light touch, and
 proprioception).

 -  Evidence of inflammatory arthritis on exam and/or HLA-B27 positive (flow cytometry).

 -  Allergy or prior intolerance to any of the following antibiotics: azithromycin,
 fluoroquinolones, or penicillin.

 -  Fewer than 3 stools per week or more than 3 stools per day as the usual frequency,
 loose or liquid stools other than on an occasional basis.

 -  Regular use of laxatives or any agent that increases gastric pH (regular defined as at
 least weekly).

 -  Have household contacts who are <2 years old or >80 years old or infirmed or
 immunocompromised (for reasons including corticosteroid therapy, HIV infection, cancer
 chemotherapy, or other chronic debilitating disease).

 -  Employment as either a health care worker with direct patient care, in a daycare
 center (for children or the elderly), or working directly with food.

 -  History of microbiologically confirmed Campylobacter infection

 -  Immunologic evidence of Campylobacter exposure

 -  Individuals who have traveled to countries with high Campylobacter rates within the
 past two years and who experienced an episode of diarrhea during or within 1 week of
 returning from their trip.

 -  And others