A Double-Blind Placebo-Control Dose Escalating Study to Evaluate the Safety and Immunogenicity of dmLT by Oral, Sublingual and Intradermal Vaccination in Adults Residing in an Endemic Area

This is a Phase 1 double‐blinded, placebo‐controlled, dose‐escalation trial to evaluate the safety and immunogenicity of double mutant heat‐labile toxin LTR192G/L211A (dmLT) from Enterotoxigenic Escherichia coli (ETEC) by oral, sublingual, or intradermal vaccination in approximately 135 healthy adult volunteers, age 18‐45 years, who meet all the eligibility criteria and reside in Bangladesh. Study duration is approximately 2.5 years, with each participant duration for up to 9 months depending on the route of dmLT administered. The study population will be recruited from Mirpur, a community of Dhaka, Bangladesh, known as having a high rate of diarrheal, respiratory and enteric disease. This clinical trial is designed to assess the safety, reactogenicity, tolerability, and immunogenicity of a range of dosages of dmLT administered by three different routes: oral, sublingual, or intradermal. The oral and sublingual routes of administration will evaluate dosages of 5, 25, and 50 micrograms of dmLT; the intradermal route of administration will evaluate dosages of 0.3, 1.0, and 2.0 micrograms of dmLT. Participants will receive a total of three sequential doses of dmLT; the oral and sublingual routes will be at days 1, 15, and 29 and the intradermal route will be at days 1, 22, and 43. There is no specific hypothesis being tested in this study. The primary objective of this study is to assess the reactogenicity, safety, and tolerability of dmLT when administered in three sequential doses, over a range of dosages by oral, sublingual, or intradermal routes. The secondary objectives of this study are 1) to assess the long‐term safety, from first vaccination through 6 months following the last dose of vaccine, 2) to evaluate the serum anti‐dmLT IgG and IgA response, 3) to evaluate the IgG and IgA anti‐dmLT Antibody Secreting Cell (ASC) response, 4) to evaluate the IgG and IgA anti‐dmLT Antibodies in Lymphocyte Supernatant (ALS) response, 5) to evaluate the total fecal IgA and fecal anti‐dmLT IgA response, and 6) to evaluate the total salivary IgA and the saliva‐derived anti‐dmLT IgA response.