Safety and immunogenicity in humans of enterotoxigenic Escherichia coli double mutant heat-labile toxin administered intradermally
Year: 2025
Type: article
Abstract: Enterotoxigenic Escherichia coli (ETEC) diarrhea is associated with a high burden of disease globally, for which no licensed vaccine is available. A Phase 1, double-blind, dose-escalation (0.1-2.0 µg) study was conducted to evaluate the safety and immunogenicity of double mutant heat-labile toxin LTR192G/L211A (dmLT) delivered intradermally (ID) to healthy adults. Subjects received up to three immunizations at three-week intervals. The vaccine was safe, although it induced mild local and some gastrointestinal adverse events, as well as frequent hyperpigmentation at the injection site. High levels of serum IgG and IgA, LT neutralizing antibodies, and IgG and IgA antibodies in lymphocyte supernatant were elicited post-vaccination, most prominently at the largest dose (2.0 μg). Rates of responses were the highest in subjects who received the largest dose (2.0 μg) and multiple immunizations. The ETEC dmLT vaccine was safe and highly immunogenic, inducing long-lasting systemic and mucosal responses when administered by the ID route. Trial registration Clinical Trials NCT02531685.
Source: npj Vaccines
Institutions: University of Maryland, Baltimore, Program for Appropriate Technology in Health, Emmes (United States), Cincinnati Children's Hospital Medical Center, University of Cincinnati, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Johns Hopkins University
Language: English
Subfield: Endocrinology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,890
Funders: U.S. Department of Health and Human Services, Bill and Melinda Gates Foundation, Cincinnati Children's Hospital Medical Center, National Institutes of Health, National Cancer Institute, National Institute of Allergy and Infectious Diseases, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases
Awards: G1966383608, G2948059169, G2983863764, G3340512627, G3374619110, G3702640434, G4090000783, G5122588083, G5740792172, G5917853598, G6528419944, G6651476754, Immune Mechanisms of Protection in S. Typhi Infection and Vaccination in Humans, PATH - to advance the development and evaluation of the promising new dmLT adjuvant by ensuring an expanded supply of high-quality clinical-grade material..., G821304228, Mechanisms of Mucosal and Systemic Immunity to Vaccination and Infection with Enteric Pathogens in Children and Adults, UNIVERSITY OF MARYLAND GREENEBAUM CANCER CENTERSUPPORT GRANT
OpenAlex ID: W4407062818