Evaluation of the safety and immunogenicity of the oral inactivated multivalent enterotoxigenic Escherichia coli vaccine ETVAX in Bangladeshi adults in a double-blind, randomized, placebo-controlled Phase I trial using electrochemiluminescence and ELISA assays for immunogenicity analyses

• DOI: 10.1016/j.vaccine.2018.11.040
• Publication Date: 2018-11-22T22:49:28Z
• Authors: Marjahan Akhtar; Mohiul I. Chowdhury; Taufiqur R. Bhuiyan; Joanna Kaim; Tasnuva Ahmed; Tanzeem A. Rafique; Arifuzzaman Khan; Sadia I.A. Rahman; Farhana Khanam; Yasmin A. Begum; Mir Z. Sharif; Laila N. Islam; Nils Carlin; Nicole Maier; Alan Fix; Thomas F. Wierzba; Richard I. Walker; A. Louis Bourgeois; Ann-Mari Svennerholm; Firdausi Qadri; Anna Lundgren
• Keywords: Enterotoxigenic Escherichia coli; Toxoid; Immunoglobulin A

The safety and immunogenicity of the second generation oral enterotoxigenic Escherichia coli (ETEC) vaccine ETVAX, consisting inactivated recombinant E. strains over-expressing colonization factors (CFs) CFA/I, CS3, CS5 CS6 heat labile toxoid LCTBA, were evaluated in Bangladeshi volunteers. To enable analysis antibody responses against multiple antigens for subsequent use small sample volumes from children, a sensitive electrochemiluminescence (ECL) assay intestine-derived antibody-secreting cell using antibodies lymphocyte secretions (ALS) was established Meso Scale Discovery technology. Three groups adults (n = 15 per group) received two doses ETVAX with or without double mutant LT (dmLT) adjuvant placebo initial part randomized, double-blind, placebo-controlled, age-descending, dose-escalation trial. CF- LTB-specific ALS plasma IgA analyzed by ECL and/or ELISA. safe well tolerated adults. Magnitudes determined ELISA correlated (r 0.85 to 0.98 five primary antigens, P < 0.001) selected as readout method. each detected 87–100% vaccinees after first 100% dose. Plasma different CFs LTB observed 62–93% vaccinees, respectively. No statistically significant effect dmLT on any antigen detected, but overall antigenic breadth response tended favor adjuvanted when 4 more 5 considered. Responses recipients infrequent mainly single antigens. promising results supported testing descending age children. ClinicalTrials.gov Identifier: NCT02531802.