Safety and immunogenicity in humans of enterotoxigenic Escherichia coli double mutant heat-labile toxin administered intradermally
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.
Authors
- Cassandra Ballou (ORCID: https://orcid.org/0000-0003-0097-5599)
- Marcelo B. Sztein (ORCID: https://orcid.org/0000-0001-8282-860X)
- A. Louis Bourgeois (ORCID: https://orcid.org/0000-0001-8952-5302)
- Michelle Dickey
- Rebecca C. Brady (ORCID: https://orcid.org/0000-0002-7635-6172)
- Jessica Butts
- Nicole Maier (ORCID: https://orcid.org/0000-0001-5573-4843)
- Jessica A. White (ORCID: https://orcid.org/0000-0003-1932-6345)
- Marcela F. Pasetti (ORCID: https://orcid.org/0000-0003-0894-4009)
- David I. Bernstein (ORCID: https://orcid.org/0000-0002-0100-1991)
- Shahida Baqar
- Patricia L. Milletich
Institutions
- University of Maryland, Baltimore (US)
- Cincinnati Children's Hospital Medical Center (US)
- Program for Appropriate Technology in Health (US)
- Johns Hopkins University (US)
- Emmes (United States) (US)
- National Institute of Allergy and Infectious Diseases (US)
- University of Cincinnati Medical Center (US)
Publication Details
- Journal
- npj Vaccines
- Published
- 2025-02-01
- DOI
- https://doi.org/10.1038/s41541-025-01071-7
- Citations
- 4
- Primary Topic
- Escherichia coli research studies
- Type
- article
- Field-Weighted Citation Impact
- 7.19
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 Institute of Allergy and Infectious Diseases
- Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases