ETEC Logistics Trial (TREK) (Trek)

• Incidence of Enterotoxigenic Escherichia coli (ETEC) illness defined as a diarrheal episode associated with an LT, LT/ST, or ST-positive ETEC strain isolated from a sample of a stool [ Time Frame: during the diarrheal episode or within 48 hours after the last stool in the diarrheal episode. ] [ Designated as safety issue: No ]
• Safety of heat-labile enterotoxin of Escherichia coli (LT) delivered by transcutaneous immunization (TCI) vs placebo [ Time Frame: From vaccination 1 to completion of Day 180 follow-up, about a seven month time period ] [ Designated as safety issue: Yes ]

• Incidence of Enterotoxigenic Escherichia coli (ETEC) illness defined as a diarrheal episode associated with an LT, LT/ST, or ST-positive ETEC strain isolated from a sample of a stool [ Time Frame: during the diarrheal episode or within 48 hours after the last stool in the diarrheal episode. ]
• Safety of heat-labile enterotoxin of Escherichia coli (LT) delivered by transcutaneous immunization (TCI) vs placebo [ Time Frame: From vaccination 1 to completion of Day 180 follow-up, about a seven month time period ]

• Stool frequency per episode of ETEC illness in placebo recipients [ Time Frame: Duration of stay in Mexico or Guatemala assessed up to four weeks ] [ Designated as safety issue: No ]
• Immunogenicity of LT delivered by TCI [ Time Frame: at least three weeks prior to arrival in country, arrival in Mexico or Guatemala, and 5 to 18 days after arrival ] [ Designated as safety issue: No ]
• Incidence of irritable bowel syndrome following travel to areas of ETEC endemnicity. [ Time Frame: Baseline through six months post return from Latin America. A period of about six months. ] [ Designated as safety issue: No ]
• Incidence of vaccine preventable outcome in placebo and LT patch recipients. [ Time Frame: Duration of each individual participant stay in Mexico or Guatemala ranging from 7 to 28 Days. ] [ Designated as safety issue: No ]

• Stool frequency per episode of ETEC illness in placebo recipients [ Time Frame: Duration of stay in Mexico or Guatemala assessed up to four weeks ]
• Immunogenicity of LT delivered by TCI [ Time Frame: at least three weeks prior to arrival in country, arrival in Mexico or Guatemala, and 5 to 18 days after arrival ]
• Incidence of irritable bowel syndrome following travel to areas of ETEC endemnicity. [ Time Frame: Baseline through six months post return from Latin America. A period of about six months. ]
• Incidence of vaccine preventable outcome in placebo and LT patch recipients. [ Time Frame: Duration of each individual participant stay in Mexico or Guatemala ranging from 7 to 28 Days. ]

This is a multicenter, double-blind, randomized, placebo-controlled field trial to evaluate the epidemiology of natural infection with ETEC occurring after transcutaneous immunization in a field setting.

The primary objectives of the study are to evaluate the incidence of ETEC illness in a field setting and to compare the safety of LT delivered by TCI with placebo. The secondary objectives include, but are not limited to:

evaluate the stool frequency per episode of ETEC illness in placebo recipients, to evaluate the immunogenicity of LT delivered by TCI, to evaluate the incidence of IBS following travel to areas of ETEC endemnicity, and to evaluate the incidence of VPO in placebo and LT patch recipients.

• Biological: Heat-Labile Enterotoxin of Escherichia coli (LT)
  Subjects in Group 1 will receive two vaccinations of a patch containing 37.5µg LT 2 to 3 weeks apart.
• Biological: Placebo
  The placebo patch contains all of the components of the active patch, but with no LT included in the formulation.

• Active Comparator: Group 1
  Group 1 subjects will receive two vaccinations via transcutaneous immunization (TCI), 14 to 21 days apart, with a patch containing 37.5µg LT
  Intervention: Biological: Heat-Labile Enterotoxin of Escherichia coli (LT)
• Placebo Comparator: Group 2
  Group 2 subjects will receive two vaccinations via transcutaneous immunization (TCI), 14 to 21 days apart, with a patch containing 0µg LT (placebo patch containing no LT)
  Intervention: Biological: Placebo

Inclusion Criteria:

• Healthy adult men and women 18-64 years of age inclusive at screening
• Signed Informed Consent form
• Planned travel to an area within 2 ½ hours traveling distance of Cuernavaca or Guadalajara, Mexico or Antigua, Guatemala (minimum stay of 7 days)
• If female who is not post-menopausal or surgically sterile, negative pregnancy test (within 24 hours prior to vaccination) and agreement to employ an effective form of birth control or practice abstinence through the end of the study.

Exclusion Criteria:

• Clinically significant abnormalities as determined by the Investigator/clinician during physical inspection
• Received investigational product from 30 days before date of first vaccination or during the entire study period
• Ever received LT, ETEC, or cholera vaccine
• History of traveler's diarrhea within the previous year
• Travel to a developing country within the last year
• Women who are pregnant or breastfeeding
• History of achlorhydria
• Evidence of immunosuppression, including concomitant immunosuppressive therapy; fever > 99.5°F (37.5°C) on day of vaccination
• Current problems with alcohol or substance abuse
• An employee of the study clinic
• Sensitivity or allergy to any of the vaccine components
• History of significant blood loss, blood product donation, or blood product recipient in the previous 60 days
• Planned use of Imodium or antibiotics for self treatment of diarrhea during the study period
• Visible tattoos or marks (tattoos/scars) at the vaccination areas that would prevent appropriate dermatologic monitoring of the vaccination sites; and
• Medical history of acute or chronic GI illness or major GI surgery.